StemCell Therapy

NEW YORK, Nov. 28, 2019 /PRNewswire/ --

INTRODUCTIONOver the last 12 months, the pharmaceutical industry reported a year-on-year increment of nearly 75% in funding to support the development of various cell and gene therapies. In fact, close to USD 5 billion has been invested into research on gene-based therapies in the previous two decades. Interestingly, over 2,600 clinical studies have been initiated in this field of research, since 1989. The aforementioned numbers are indicative of the rapid pace of development in this upcoming segment of the biopharmaceutical industry. The development of such therapy products require gene delivery vehicles, called vectors, to desired locations within the body (in vivo) / specific cells (ex vivo). The growing demand for such therapies and the rising number of clinical research initiatives in this domain has led to an increase in demand for preclinical and clinical grade gene delivery vectors. Fundamentally, genetic modifications can be carried out using either viral (such as adenovirus, adeno associated virus (AAV), lentivirus, retrovirus, Sendai virus, herpes simplex virus, vaccinia virus, baculovirus and alphavirus) or non-viral (such as plasmid DNA) vectors. Moreover, recent advances in vector research have led to the development of several innovative viral / non-viral gene delivery approaches.

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At present, 10+ genetically modified therapies have received approval / conditional approval in various regions of the world; these include (in the reverse chronological order of year of approval) Zynteglo (2019), Zolgensma (2019), Collategene (2019), LUXTURNA (2017), YESCARTA (2017), Kymriah (2017), INVOSSA (2017), Zalmoxis (2016), Strimvelis (2016), Imlygic (2015), Neovasculagen (2011), Rexin-G (2007), Oncorine (2005) and Gendicine (2003). In addition, over 500 therapy candidates are being investigated across different stages of development. The growing number of gene-based therapies, coupled to their rapid progression through the drug development process, has created significant opportunities for companies with expertise in vector manufacturing. Presently, a number of industry (including both well-established companies and smaller R&D-focused initiatives), and non-industry players (academic institutes) claim to be capable of manufacturing different types of viral and non-viral vectors. In addition, there are several players offering novel technology solutions, which are capable of improving existing genetically modified therapy products and upgrading their affiliated manufacturing processes. Considering prevalent and anticipated future trends, we believe that the vector and gene therapy manufacturing market is poised to grow steadily, driven by a robust pipeline of therapy candidates and technical advances aimed at mitigating existing challenges related to gene delivery vector and advanced therapy medicinal products.

SCOPE OF THE REPORTThe "Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market (3rd Edition), 2019-2030 (Focus on AAV, Adenoviral, Lentiviral, Retroviral, Plasmid DNA and Other Vectors)" report features an extensive study of the rapidly growing market of viral and non-viral vector and gene therapy manufacturing, focusing on contract manufacturers, as well as companies with in-house manufacturing facilities. The study presents an in-depth analysis of the various firms / organizations that are engaged in this domain, across different regions of the globe. Amongst other elements, the report includes: An overview of the current status of the market with respect to the players involved (both industry and non-indutry) in manufacturing viral vectors, non-viral vectors and other novel types of vectors. It features information on the year of establishment, scale of production, type of vectors manufactured, location of manufacturing facilities, applications of vectors (in gene therapy, cell therapy, vaccines and others), and purpose of production (fulfilling in-house requirements / for contract services). An informed estimate of the annual demand for viral and non-viral vectors, taking into account the marketed gene-based therapies and clinical studies evaluating vector-based therapies; the analysis also takes into consideration various relevant parameters, such as target patient population, dosing frequency and dose strength. An estimate of the overall, installed vector manufacturing capacity of industry players based on information available in the public domain, and insights generated via both secondary and primary research. The analysis also highlights the distribution of the global capacity by vector type (viral vector and plasmid DNA), scale of operation (clinical and commercial), size of the company / organization (small-sized, mid-sized and large) and key geographical regions (North America, Europe, Asia Pacific and the rest of the world). An in-depth analysis of viral vector and plasmid DNA manufacturers, featuring three schematic representations; namely [A] a three dimensional grid analysis, representing the distribution of vector manufacturers (on the basis of type of vector) across various scales of operation and purpose of production (in-house operations and contract manufacturing services), [B] a logo landscape of viral vector and plasmid DNA manufacturers based on the type (industry and non-industry) and the size of the industry player (small-sized, mid-sized and large companies), and [C] a schematic world map representation, highlighting the geographical locations of vector manufacturing hubs. An analysis of recent collaborations and partnership agreements inked in this domain since 2015; it includes details of deals that were / are focused on the manufacturing of vectors, whihc were analyzed on the basis of year of agreement, type of agreement, type of vector involved, and scale of operation (laboratory, clinical and commercial). An analysis of the various factors that are likely to influence the pricing of vectors, featuring different models / approaches that may be adopted by product developers / manufacturers in order to decide the prices of proprietary vectors. An overview of other viral / non-viral gene delivery approaches that are currently being researched for the development of therapies involving genetic modification. Elaborate profiles of key players based in North America, Europe and Asia-Pacific (shortlisted based on scale of operation). Each profile features an overview of the company / organization, its financial performance (if available), information on its manufacturing facilities, vector manufacturing technology and an informed future outlook. A discussion on the factors driving the market and the various challenges associated with the vector production process.

One of the key objectives of this report was to evaluate the current market size and the future opportunity associated with the vector manufacturing market, over the coming decade. Based on various parameters, such as the likely increase in number of clinical studies, anticipated growth in target patient population, existing price variations across different vector types, and the anticipated success of gene therapy products (considering both approved and late-stage clinical candidates), we have provided an informed estimate of the likely evolution of the market in the short to mid-term and long term, for the period 2019-2030. In order to provide a detailed future outlook, our projections have been segmented on the basis of [A] type of vectors (AAV vector, adenoviral vector, lentiviral vector, retroviral vector, plasmid DNA and others), [B] applications (gene therapy, cell therapy and vaccines), [C] therapeutic area (oncological disorders, inflammation & immunological diseases, neurological disorders, ophthalmic disorders, muscle disorders, metabolic disorders, cardiovascular disorders and others), [D] scale of operation (preclinical, clinical and commercial) and [E] geography (North America, Europe, Asia Pacific and rest of the world).

The research, analysis and insights presented in this report are backed by a deep understanding of key insights generated from both secondary and primary research. For the purpose of the study, we invited over 160 stakeholders to participate in a survey to solicit their opinions on upcoming opportunities and challenges that must be considered for a more inclusive growth. Our opinions and insights presented in this study were influenced by discussions held with several key players in this domain. The report features detailed transcripts of interviews held with the stakeholders: Menzo Havenga (Chief Executive Officer and President, Batavia Biosciences) Nicole Faust (Chief Executive Officer & Chief Scientific Officer, CEVEC Pharmaceuticals) Jeffrey Hung (Chief Commercial Officer, Vigene Biosciences) Olivier Boisteau, (Co-Founder / President, Clean Cells), Laurent Ciavatti (Business Development Manager, Clean Cells) and Xavier Leclerc (Head of Gene Therapy, Clean Cells) Joost van den Berg (Director, Amsterdam BioTherapeutics Unit) Bakhos A Tannous (Director, MGH Viral Vector Development Facility, Massachusetts General Hospital) Colin Lee Novick (Managing Director, CJ Partners) Cedric Szpirer (Executive & Scientific Director, Delphi Genetics) Semyon Rubinchik (Scientific Director, ACGT) Alain Lamproye (President of Biopharma Business Unit, Novasep) Astrid Brammer (Senior Manager Business Development, Richter-Helm) Brain M Dattilo (Business Development Manager, Waisman Biomanufacturing) Marco Schmeer (Project Manager, Plasmid Factory) and Tatjana Buchholz (Marketing Manager, Plasmid Factory) Nicolas Grandchamp (R&D Leader, GEG Tech)

All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.

RESEARCH METHODOLOGYThe data presented in this report has been gathered via secondary and primary research. For all our projects, we conduct interviews with experts in the area (academia, industry, medical practice and other associations) to solicit their opinions on emerging trends in the market. This is primarily useful for us to draw out our own opinion on how the market may evolve across different regions and technology segments. Wherever possible, the available data has been checked for accuracy from multiple sources of information.

The secondary sources of information include: Annual reports Investor presentations SEC filings Industry databases News releases from company websites Government policy documents Industry analysts' views

While the focus has been on forecasting the market over the period 2019-2030, the report also provides our independent view on various technological and non-commercial trends emerging in the industry. This opinion is solely based on our knowledge, research and understanding of the relevant market gathered from various secondary and primary sources of information.

CHAPTER OUTLINESChapter 2 is an executive summary of the insights captured in our research. The summary offers a high-level view on the likely evolution of the vector and gene therapy manufacturing market in the short to mid-term, and long term.

Chapter 3 is a general introduction to the various types of viral and non-viral vectors. It includes a detailed discussion on the design, manufacturing requirements, advantages, limitations and applications of currently available gene delivery vehicles. The chapter also provides a brief description of the clinical and approved pipeline of genetically modified therapies. Further, it includes a review of the latest trends and innovations in the contemporary vector manufacturing market.

Chapter 4 provides a detailed overview of around 80 companies, featuring both contract service providers and in-house manufacturers that are actively involved in the production of viral vectors and / or gene therapies utilizing viral vectors. The chapter provides details on the year of establishment, scale of production, type of viral vectors manufactured (AAV, adenoviral, lentiviral, retroviral and others), location of manufacturing facilities, applications of vectors (gene therapies, cell therapies, vaccines and others) and purpose of production (fulfilling in-house requirements / for contract services).

Chapter 5 provides an overview of around 30 industry players that are actively involved in the production of plasmid DNA and other non-viral vectors and / or gene therapies utilizing non-viral vectors. The chapter provides details on the year of establishment, scale of production, location of manufacturing facilities, applications of vectors (gene therapies, cell therapies, vaccines and others) and purpose of vector production (fulfilling in-house requirements / for contract services).

Chapter 6 provides an overview of around 80 non-industry players (academia and research institutes) that are actively involved in the production of vectors (both viral and non-viral) and / or gene therapies. The chapter provides details on the year of establishment, scale of production, location of manufacturing facilities, type of vectors manufactured (AAV, adenoviral, lentiviral, retroviral, plasmid DNA and others), applications of vectors (gene therapies, cell therapies, vaccines and others) and purpose of vector production (fulfilling in-house requirements / for contract services).

Chapter 7 features detailed profiles of the US based contract service providers / in-house manufacturers that possess commercial scale capacities for the production of viral vectors / plasmid DNA. Each profile presents a brief overview of the company, its financial information (if available), details on vector manufacturing facilities, manufacturing experience and an informed future outlook.

Chapter 8 features detailed profiles of EU based contract service providers / in-house manufacturers that possess commercial scale capacities for the production of viral vectors / plasmid DNA. Each profile presents a brief overview of the company, its financial information (if available), details on vector manufacturing facilities, manufacturing experience, and an informed future outlook.

Chapter 9 features detailed profiles of Asia-Pacific based contract service provider(s) / in-house manufacturer(s) that possess commercial scale capacities for production of viral vectors / plasmid DNA. Each profile presents a brief overview of the company, its financial information (if available), details on vector manufacturing facilities, manufacturing experience, and an informed future outlook.

Chapter 10 provides detailed information on other viral / non-viral vectors (including alphavirus vectors, Bifidobacterium longum vectors, Listeria monocytogenes vectors, myxoma virus based vectors, Sendai virus based vectors, self-complementary vectors (improved versions of AAV), and minicircle DNA and Sleeping Beauty transposon vectors (non-viral gene delivery approach)) that are currently being utilized by pharmaceutical players to develop gene therapies, T-cell therapies and certain vaccines, as well. This chapter presents overview on all the aforementioned types of vectors, along with examples of companies that use them in their proprietary products. It also includes examples of companies that are utilizing specific technology platforms for the development / manufacturing of some of these novel vectors.

Chapter 11 features an elaborate analysis and discussion of the various collaborations and partnerships related to the manufacturing of vectors or gene therapies, which have been inked amongst players. It includes a brief description of the purpose of the partnership models (including licensing agreements, mergers / acquisitions, product development, service alliances, manufacturing, and others) that have been adopted by the stakeholders in this domain, since 2015. It consists of a schematic representation showcasing the players that have forged the maximum number of alliances. Furthermore, we have provided a world map representation of the deals inked in this field, highlighting those that have been established within and across different continents.

Chapter 12 presents a collection of key insights derived from the study. It includes a grid analysis, highlighting the distribution of viral vectors and plasmid DNA manufacturers on the basis of their scale of production and purpose of manufacturing (fulfilling in-house requirement / contract service provider). In addition, it consists of a logo landscape, representing the distribution of viral vector and plasmid DNA manufacturers based on the type of organization (industry / non-industry) and size of employee base. The chapter also consists of six world map representations of manufacturers of viral / non-viral vectors (lentiviral, adenoviral, AAV and retroviral vectors, and plasmid DNA), depicting the most active geographies in terms of the presence of the organizations. Furthermore, we have provided a schematic world map representation to highlight the locations of global vector manufacturing hubs across different continents.

Chapter 13 highlights our views on the various factors that may be taken into consideration while pricing viral vectors / plasmid DNA. It features discussions on different pricing models / approaches that manufacturers may choose to adopt to decide the prices of their proprietary products.

Chapter 14 features an informed estimate of the annual demand for viral and non-viral vectors, taking into account the marketed gene-based therapies and clinical studies evaluating vector-based therapies. This section offers an opinion on the required scale of supply (in terms of vector manufacturing services) in this market. For the purpose of estimating the current clinical demand, we considered the active clinical studies of different types of vector-based therapies that have been registered till date. The data was analysed on the basis of various parameters, such as number of annual clinical doses, trial location, and the enrolled patient population across different geographies. Further, in order to estimate the commercial demand, we considered the marketed vector-based therapies, based on various parameters, such as target patient population, dosing frequency and dose strength.

Chapter 15 features an informed analysis of the overall installed capacity of the vectors and gene therapy manufacturers. The analysis is based on meticulously collected data (via both secondary and primary research) on reported capacities of various small-sized, mid-sized and large companies, distributed across their respective facilities. The results of this analysis were used to establish an informed opinion on the vector production capabilities of the organizations across different types of vectors (viral vectors, plasmid DNA, and both), scale of operation (clinical and commercial) and geographies (North America, EU, Asia-Pacific and the rest of the world).

Chapter 16 presents a comprehensive market forecast analysis, highlighting the likely growth of vector and gene therapy manufacturing market till the year 2030. We have segmented the financial opportunity on the basis of [A] type of vectors (AAV vector, adenoviral vector, lentiviral vector, retroviral vector, plasmid DNA and others), [B] applications (gene therapy, cell therapy and vaccines), [C] therapeutic area (oncological disorders, inflammation & immunological diseases, neurological disorders, ophthalmic disorders, muscle disorders, metabolic disorders, cardiovascular disorders and others), [D] scale of operation (preclinical, clinical and commercial) and [E] geography (North America, Europe, Asia Pacific and rest of the world). Due to the uncertain nature of the market, we have presented three different growth tracks outlined as the conservative, base and optimistic scenarios.

Chapter 17 provides details on the various factors associated with popular viral vectors and plasmid DNA that act as market drivers and the various challenges associated with the production process. This information has been validated by soliciting the opinions of several industry stakeholders active in this domain.

Chapter 18 presents insights from the survey conducted on over 160 stakeholders involved in the development of different types of gene therapy vectors. The participants, who were primarily Director / CXO level representatives of their respective companies, helped us develop a deeper understanding on the nature of their services and the associated commercial potential.

Chapter 19 summarizes the entire report. The chapter presents a list of key takeaways and offers our independent opinion on the current market scenario and evolutionary trends that are likely to determine the future of this segment of the industry.

Chapter 20 is a collection of transcripts of the interviews conducted with representatives from renowned organizations that are engaged in the vector and gene therapy manufacturing domain. In this study, we spoke to Menzo Havenga (Chief Executive Officer and President, Batavia Biosciences), Nicole Faust (Chief Executive Officer & Chief Scientific Officer, CEVEC Pharmaceuticals), Jeffrey Hung (Chief Commercial Officer, Vigene Biosciences), Olivier Boisteau, (Co-Founder / President, Clean Cells) and Xavier Leclerc (Head of Gene Therapy, Clean Cells), Laurent Ciavatti (Business Development Manager, Clean Cells), Joost van den Berg (Director, Amsterdam BioTherapeutics Unit), Bakhos A Tannous (Director, MGH Viral Vector Development Facility, Massachusetts General Hospital), Colin Lee Novick (Managing Director, CJ Partners), Cedric Szpirer (Executive & Scientific Director, Delphi Genetics), Semyon Rubinchik (Scientific Director, ACGT), Alain Lamproye (President of Biopharma Business Unit, Novasep), Astrid Brammer (Senior Manager Business Development, Richter-Helm), Brain M Dattilo (Business Development Manager, Waisman Biomanufacturing), Marco Schmeer (Project Manager, Plasmid Factory) and Tatjana Buchholz (Marketing Manager, Plasmid Factory), and Nicolas Grandchamp (R&D Leader, GEG Tech).

Chapter 21 is an appendix, which provides tabulated data and numbers for all the figures in the report.

Chapter 22 is an appendix that provides the list of companies and organizations that have been mentioned in the report.

Read the full report: https://www.reportlinker.com/p05828868/?utm_source=PRN

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Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market (3rd Edition), 2019-2030 (Focus on AAV, Adenoviral, Lentiviral, Retroviral,...

UK cell and gene therapy firms are worried a shortage of skilled manufacturing staff will slow growth with some concerned Brexit will exacerbate the problem.

The findings come from a new skills survey by the Cell and Gene Therapy Catapult (CGTC) an organisation set up to support the sector by non-departmental government body, Innovate UK.

Of the 41 companies that responded, 98% said they planned to expand their headcount over the next five years. Of these, 83% raised concerns that hiring and retaining skilled staff will be an issue for growth.

Image: iStock/philhol

In addition, some respondents were concerned that Brexit will have a negative impact on recruiting and retaining skilled non-UK EU people according to the report.

More than 1,700 people are employed in bioprocessing roles in the UK cell and gene therapy sector, which is up from the 500 or so working in such positions in 2017. Based on this growth rate the CGTC expects 3,800 people will be working in such roles by 2024.

The survey also revealed 492 people are employed in cell and gene therapy manufacturing roles in the UK. This is expected to increase to 1,456 people up 196% by 2024. Respondents said finding staff with manufacturing skills as a substantial concern.

To address this, the report authors suggested cell and gene therapy firms would need to look beyond the sector.

The lack of talent will highly likely act as a brake to growth, with significant negative consequences on both organic and inward investment.

It is recommended, that companies are supported to deliver on their growth strategies, through the provision of supportive schemes, to both upskill their existing workforce as well as recruiting new talent, from outside of the sector.

The survey did not tally the number of EU nationals working in the UK cell and gene therapy sector or look at the potential impact Brexit would have on sectors ability to recruit.

However, a CGTC spokesperson told us We are confident that the UK cell and gene therapy industry will be able to source the necessary skills, and that the opportunities in research and training will remain attractive.

The spokesperson suggested overseas scientists continue to view the UK as attractive, adding We continue to see skilled people wanting to work in the UK sector from across the globe.

In addition, the spokesperson also expressed confidence cell and gene therapy developers would continue to see the UK as an attractive development and production base post withdrawal.

The supply chains for these advanced therapies are highly specialised and have been stringently developed in collaboration with medicine regulators to minimise any potential disruption.

There are already a number of advance therapies manufactured in the UK and exported seamlessly to the US for clinical trials and vice versa, we are confident that the movement of these therapies will remain unimpeded.

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Lack of UK cell and gene therapy skills a concern - Bioprocess Insider - BioProcess Insider

(Reuters) - Blackstone Group Inc (BX.N) said on Monday it will invest $400 million in a joint venture with Swiss drug company Ferring that is working on an experimental gene therapy for bladder cancer, the private equity giants largest ever bet on drug development.

FILE PHOTO: The ticker and trading information for Blackstone Group is displayed at the post where it is traded on the floor of the New York Stock Exchange (NYSE) April 4, 2016. REUTERS/Brendan McDermid

Investing in yet-to-be-approved medicines is a lucrative but also risky proposition for buyout firms, and only few have had the stomach to place such bets. Blackstone made its foray in the sector last year, acquiring Clarus, an investment firm specializing in life sciences.

For its part, Ferring will invest $170 million in the joint venture with Blackstone, dubbed FerGene, bringing its total funding to $570 million, the companies said in a statement.

FerGene is developing a gene therapy for bladder cancer patients with an aggressive form of the disease whose current options include having their bladder removed. The treatment works by entering the walls of the bladder where it releases a gene to trigger the patients own body to make a protein to fight off cancer.

We believe, and Ferring also believes, that this can change the standard of care in bladder cancer, a terrible disease, Nicholas Galakatos, senior managing director of Blackstone Life Sciences, said in an interview.

Oncology is a new area for Ferring, but it is one that we as Blackstone Life Sciences have a lot of experience in

The team assembled by Blackstone has worked at several of the worlds largest cancer drugmakers, including Roche unit Genentech, Merck & Co Inc (MRK.N), and Millennium Pharmaceuticals, now a part of Takeda Pharmaceutical Co Ltd (4502.T).

To minimize its risk, Blackstone invests in the late stages of drug development, when a medicine has already gone through important milestones. Late-stage drug development can also be expensive because of the clinical trials involved, something that Blackstone is seeking to capitalize on by partnering with pharmaceutical firms looking to share the cost burden.

FerGenes therapy, named nadofaragene firadenovec, is currently in the final stage of clinical research, results from which will be presented on Dec. 5 at the Society of Urologic Oncologys annual meeting.

Since it launched its life sciences unit, Blackstone has also formed a new company with Novartis AG (NOVN.S) to study a type of heart drug. Blackstone invested $250 million in that venture.

Reporting by Rebecca Spalding in New York; Editing by Alistair Bell

Original post:
Blackstone to invest $400 million in gene therapy venture with Ferring - Reuters

A research scientist at a laboratory of a pharmaceutical company in US. Reuters

The full scope of Novartis $500 million plan, revealed to Reuters in an interview with the companys gene therapy chief, has not been previously disclosed. It is second only to Pfizer, which has allocated $600 million to build its own gene therapy manufacturing plants, according to filings and interviews with industry executives.

Gene therapies aim to correct certain diseases by replacing the missing or mutated version of a gene found in a patients cells with healthy copies. With the potential to cure devastating illnesses in a single dose, drugmakers say they justify prices well above $1 million per patient.

But the treatments are also extremely complex to make, involving the cultivation of living material, and still pose a risk of serious side effects.

Drugmakers say building their own manufacturing plants is a response to rising costs and delays associated with relying on third-party contract manufacturers, which are also expanding to capitalise on demand. They say owning their own facilities helps safeguard proprietary production methods and more effectively address any concerns raised by the US Food and Drug Administration (FDA), which is keeping a close eye on manufacturing standards.

Theres so little capacity and capability at contract manufacturers for the novel gene therapy processes being developed by companies, said David Lennon, president of AveXis, Novartiss gene therapy division. We need internal manufacturing capabilities in the long term.

The approach is not without risks.

Bob Smith, senior vice president of Pfizers global gene therapy business, acknowledged drugmakers take a leap of faith when they make big capital investment outlays for treatments before they have been approved or, in some cases, even produced data demonstrating a benefit.

The rewards are potentially great, however.

Gene therapy is one of the hottest areas of drug research and, given the life-changing possibilities, the FDA is helping to speed treatments to market.

It has approved two so far, including Novartiss Zolgensma treatment for a rare muscular disorder priced at $2 million, and expects 40 new gene therapies to reach the US market by 2022.

There are currently several hundred under development by around 30 drugmakers for conditions from hemophilia to Duchenne muscular dystrophy and sickle cell anemia.

The proliferation of these treatments is pushing the limits of the industrys existing manufacturing capacity.

Developers of gene therapies that need to outsource manufacturing face wait times of about 18 months to get a production slot, company executives told Reuters.

They are also charged fees to reserve space that run into millions of dollars, more than double the cost of a few years ago, according to gene therapy developer RegenxBio.

As a result, companies including bluebird bio, PTC Therapeutics and Krystal Biotech are also investing in gene therapy manufacturing, according to a Reuters analysis of public filings and executive interviews.

They follow Biomarin Pharmaceutical, developer of a gene therapy for hemophilia, which constructed one of the industrys largest manufacturing facilities in 2017. The FDA is keeping a close eye on standards.

This comes amid the agencys disclosure in August that it is investigating alleged data manipulation by former executives at Novartis AveXis unit.

AveXis had switched its method for measuring Zolgensmas potency in animal studies. When results using the new method didnt meet expectations, the executives allegedly altered the data to cover it up, the FDA and Novartis have said.

One of the former executives, Brian Kaspar, denied wrongdoing in a statement to Reuters. Another, his brother Allan Kaspar, could not be reached for comment.

Novartis and the FDA say human clinical trials, which found Zolgensma effective in treating the most severe form of spinal muscular atrophy in infants, were not affected. Novartis also says its investments in gene therapy production started long before it became aware of the data manipulation allegations.

Reuters

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Pfizer and Novartis lead pharma spending spree on gene therapy - Gulf Today

Lonza and DiNAQOR AG, a global gene therapy platform company, have formed a collaboration to advance DiNAQORs preclinical programs for the treatment of cardiac myosin-binding protein-C (MYBPC3) cardiomyopathies, a genetic condition that can result in heart failure.Lonza will provide DiMAQOR preclinical, clinical and commercial production support for the companys lead preclinical program DiNA-001, an adeno-associated virus (AAV) gene therapy program for patients with MYBPC3-linked cardiomyopathy. Lonzas cell-and-gene-therapy manufacturing facility in Houston, TX will handle all product supply for DiNA-001.Through this partnership, DiNAQOR will be able to leverage Lonza's extensive, dedicated teams and laboratories for viral-vector process-development, located in Houston.In addition to its cardiac gene therapy platform, DiNAQOR is also developing a local-regional delivery system for the heart. This will allow the company to route gene therapy directly to the cardiac muscle maximizing biodistribution and transduction of the cardiomyocytes. This approach will look to minimize potential adverse effects of systemic gene therapy delivery.DiNAQOR has established an innovative gene therapy platform that will allow for the evaluation of this promising treatment for monogenic cardiomyopathies, said Alberto Santagostino, senior vice president, head of cell and gene technologies, Lonza Pharma & Biotech. DiNAQOR represents the truly trailblazing companies that we strive to empower in the cell and gene therapy space and we are fully committed to the DiNAQOR team as they seek to advance novel treatment options for people living with heart disease.Johannes Holzmeister, chairman and chief executive officer, DiNAQOR, said, Lonza is a leader in the manufacturing of adeno-associated virus gene therapy vectors and is the optimal partner to help us rapidly advance and scale the production of DiNA-001 from early-stage clinical trials through commercialization. Precise and rapid genetic diagnostics, leading analytics, and an adequate product supply for all stages of clinical development and commercialization are necessary to bring these potentially transformational gene therapies to patients suffering from heart failure. We are excited to collaborate with Lonza on this critical initiative.

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Lonza And DiNAQOR AG Enter Gene Therapy Collaboration - Contract Pharma

DetailsCategory: More NewsPublished on Wednesday, 27 November 2019 13:20Hits: 926

Collaboration will Target a Therapeutic Approach for Treating Asthma and Allergic Diseases

NEW YORK, NY, USA I November 26, 2019 I Hoth Therapeutics, Inc. (Nasdaq: HOTH) ("HOTH" or the "Company"), a biopharmaceutical company focused on developing new generation therapies for dermatological disorders such as atopic dermatitis, chronic wounds, psoriasis and acne, today announced it has entered into a licensing agreement with North Carolina State University (NC State) to study NC State's Exon Skipping Approach for Treating Allergic Diseases.

This Exon Skipping Approach was developed by Dr. Glenn Cruse, Principal Investigator and Assistant Professor in the Department of Molecular Biomedical Sciences at the NC State College of Veterinary Medicine. During Dr. Cruse's research, a new approach for the technique of antisense oligonucleotide-mediated exon skipping to specifically target and down-regulate IgE receptor expression in mast cells was identified. These findings set a breakthrough for allergic diseases as they are driven by the activation of mast cells and the release of mediators in response to IgE-directed antigens.

Mr. Robb Knie, Chief Executive Officer of Hoth, commented, "This new collaboration will allow us to leverage this invention from the renowned expertise of Dr. Glenn Cruse and his scientific team at North Carolina State University. We look forward to seeing how their work advances and what this might mean for patients suffering from undesirable steroid side effects who need an alternate treatment for asthma and other allergic diseases."

The high-affinity IgEreceptor (FcRI) plays a central role in the initiation ofallergic responses. The research project looks to target novel genes, which are critical for surface IgE receptor expression. The project will utilize splice-switching oligonucleotides (SSOs) to force expression of a truncated isoform of the target genes to reduce expression ofFcRIin mouse asthma models.

Through this collaborative project, NCSU looks to establish the most effective approach for targeting genes that regulate surface expression of FcRI in mast cells that mediate allergic airway inflammation. The study will be administering SSOs for the target genes, to optimize delivery and examine the best therapeutic approach.

About Hoth Therapeutics, Inc.Hoth Therapeutics, Inc. isa clinical-stage biopharmaceutical company focused on developing new generation therapies for dermatological disorders. HOTH's pipeline has the potential to improve the quality of life for patients suffering from indications including atopic dermatitis, chronic wounds, psoriasis, and acne. HOTH has the exclusive worldwide rights to BioLexa, the company's proprietary lead drug candidate topical platform that uniquely combines two FDA approved compounds to fight bacterial infections across multiple indications. HOTH is preparing to launch its clinical trial for the treatment of adolescent subjects, 2-17 years of age, with mild to moderate atopic dermatitis during 2020. To learn more, please visitwww.hoththerapeutics.com.

SOURCE: Hoth Therapeutics

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Hoth Therapeutics and North Carolina State University Enter License Agreement for Gene Therapy | More News | News Channels - PipelineReview.com

Expansions of DNA repeats are very hard to analyze. A method developed by researchers at the Max Planck Institute for Molecular Genetics in Berlin allows for a detailed look at these previously inaccessible regions of the genome. It combines nanopore sequencing, stem cell, and CRISPR-Cas technologies. The method could improve the diagnosis of various congenital diseases and cancers in the future.

Large parts of the genome consist of monotonous regions where short sections of the genome repeat hundreds or thousands of times. But expansions of these "DNA repeats" in the wrong places can have dramatic consequences, like in patients with Fragile X syndrome, one of the most commonly identifiable hereditary causes of cognitive disability in humans. However, these repetitive regions are still regarded as an unknown territory that cannot be examined appropriately, even with modern methods.

A research team led by Franz-Josef Mller at the Max Planck Institute for Molecular Genetics in Berlin and the University Hospital of Schleswig-Holstein in Kiel recently shed light on this inaccessible region of the genome. Mller's team was the first to successfully determine the length of genomic tandem repeats in patient-derived stem cell cultures. The researchers additionally obtained data on the epigenetic state of the repeats by scanning individual DNA molecules. The method, which is based on nanopore sequencing and CRISPR-Cas technologies, opens the door for research into repetitive genomic regions, and the rapid and accurate diagnosis of a range of diseases.A gene defect on the X chromosomeIn Fragile X syndrome, a repeat sequence has expanded in a gene called FMR1 on the X chromosome. "The cell recognizes the repetitive region and switches it off by attaching methyl groups to the DNA," says Mller. These small chemical changes have an epigenetic effect because they leave the underlying genetic information intact. "Unfortunately, the epigenetic marks spread over to the entire gene, which is then completely shut down," explains Mller. The gene is known to be essential for normal brain development. He states: "Without the FMR1 gene, we see severe delays in development leading to varying degrees of intellectual disability or autism."

Female individuals are, in most cases, less affected by the disease, since the repeat region is usually located on only one of the two X chromosomes. Since the unchanged second copy of the gene is not epigenetically altered, it is able to compensate for the genetic defect. In contrast, males have only one X chromosome and one copy of the affected gene and display the full range of clinical symptoms. The syndrome is one of about 30 diseases that are caused by expanding short tandem repeats.

First precise mapping of short tandem repeats

In this study, Mller and his team investigated the genome of stem cells that were derived from patient tissue. They were able to determine the length of the repeat regions and their epigenetic signature, a feat that had not been possible with conventional sequencing methods. The researchers also discovered that the length of the repetitive region could vary to a large degree, even among the cells of a single patient.

The researchers also tested their process with cells derived from patients that contained an expanded repeat in one of the two copies of the C9orf72 gene. This mutation leads to one of the most common monogenic causes of frontotemporal dementia and amyotrophic lateral sclerosis. "We were the first to map the entire epigenetics of extended and unchanged repeat regions in a single experiment," says Mller. Furthermore, the region of interest on the DNA molecule remained physically wholly unaltered. "We developed a unique method for the analysis of single molecules and for the darkest regions of our genome - that's what makes this so exciting for me."

Tiny pores scan single molecules

"Conventional methods are limited when it comes to highly repetitive DNA sequences. Not to mention the inability to simultaneously detect the epigenetic properties of repeats," says Bjrn Brndl, one of the first authors of the publication. That's why the scientists used Nanopore sequencing technology, which is capable of analyzing these regions. The DNA is fragmented, and each strand is threaded through one of a hundred tiny holes ("nanopores") on a silicon chip. At the same time, electrically charged particles flow through the pores and generate a current. When a DNA molecule moves through one of these pores, the current varies depending on the chemical properties of the DNA. These fluctuations of the electrical signal are enough for the computer to reconstruct the genetic sequence and the epigenetic chemical labels. This process takes place at each pore and, thus, each strand of DNA.

Genome editing tools and bioinformatics illuminate "dark matter"Conventional sequencing methods analyze the entire genome of a patient. Now, the scientists designed a process to look at specific regions selectively. Brndl used the CRISPR-Cas system to cut DNA segments from the genome that contained the repeat region. These segments went through a few intermediate processing steps and were then funneled into the pores on the sequencing chip.

"If we had not pre-sorted the molecules in this way, their signal would have been drowned in the noise of the rest of the genome," says bioinformatician Pay Giesselmann. He had to develop an algorithm specifically for the interpretation of the electrical signals generated by the repeats: "Most algorithms fail because they do not expect the regular patterns of repetitive sequences." While Giesselmann's program "STRique" does not determine the genetic sequence itself, it counts the number of sequence repetitions with high precision. The program is freely available on the internet.

Numerous potential applications in research and the clinic"With the CRISPR-Cas system and our algorithms, we can scrutinize any section of the genome - especially those regions that are particularly difficult to examine using conventional methods," says Mller, who is heading the project. "We created the tools that enable every researcher to explore the dark matter of the genome," says Mller. He sees great potential for basic research. "There is evidence that the repeats grow during the development of the nervous system, and we would like to take a closer look at this."

The physician also envisions numerous applications in clinical diagnostics. After all, repetitive regions are involved in the development of cancer, and the new method is relatively inexpensive and fast. Mller is determined to take the procedure to the next level: "We are very close to clinical application."

Reference: Giesselmann et al. 2019.Analysis of short tandem repeat expansions and their methylation state with nanopore sequencing. Nature Biotechnology.DOI: https://doi.org/10.1038/s41587-019-0293-x.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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New Device Permits a Closer Look at Previously Inaccessible Areas of the Genome - Technology Networks

Salmonella is acting up in Michigan, and it could be a model for whats happening in other states, according to a new Michigan State University study.

The study, appearing in Frontiers in Medicine, documents a substantial uptick in antibiotic resistant strains, and consequently, longer hospital stays as doctors work to treat the increasing virulent pathogens.

If you get a salmonella infection that is resistant to antibiotics today, you are more likely to be hospitalized longer, and it will take you longer to recover, said Shannon Manning, MSU Foundation professor in theDepartment of Microbiology and Molecular Genetics and senior author of the study. We need better detection methods at the clinical level to identify resistant pathogens earlier so we can treat them with the right drugs the first time.

Losing a day or more to misdiagnosis or improper treatment allows symptoms to get worse. Doctors might kill off a subpopulation of bacteria that are susceptible, but the ones that are resistant grow stronger, she added.

Salmonella is a diverse group of bacterial pathogens that causes foodborne infections. Infected patients often develop diarrhea, nausea, vomiting and abdominal pain, though some infections are more severe and can be life threatening.

When it comes to treatments, each strain reacts differently to the range of antibiotics available for prescription by doctors. So getting it right the first time is crucial.

Specifically in Michigan, doctors are seeing more strains that are resistant to ampicillin, a common antibiotic prescribed to treat salmonella. Multidrug resistance, or resistance to more than three classes of antibiotics, has also increased in Michigan and could further complicate patient treatment plans.

Were still uncertain as to why this is happening; it could be that these antibiotics have been overprescribed in human and veterinary medicine and that possessing genes for resistance has allowed these bacteria to grow and thrive in the presence of antibiotics, Manning said. Each state has its own antibiotic-resistance issues. Its important that the medical profession remains vigilant to ever-changing patterns of resistance in salmonella and other foodborne pathogens, rather than look for a blanket national solution.

Historically, salmonella has affected young children and the elderly, but now theres been a rise in adult cases, suggesting that the epidemiology of the infections has changed in Michigan.

Diving into individual strains of salmonella, the team of scientists found that patients with Typhimurium were more likely to have resistant infections as were patients infected during the fall, winter or spring months.

Another distinction was revealed between the strains affecting people living in rural and urban areas. Enteritis infections tend to be higher in rural areas. This may be attributed to rural residents exposure to farm animals or untreated sources of water.

Each states salmonella population has its own personality; so every states approach to identifying disease drivers and effective treatments should be modified to reflect these traits.

Our results show the importance of surveillance, monitoring resistance frequencies and identifying risk factors specific to each state and region, Manning said. The trends that are revealed can lead to new prevention strategies.

Additional MSU researchers contributing to the study include Sanjana Mukherjee, the lead author, Chase Anderson and Rebekah Mosci. Scientists from Wayne State, Sparrow Hospitals and the Michigan Department of Health and Human Services also contributed to this research.

(Note for media: Please include a link to the original paper in online coverage: https://www.frontiersin.org/articles/10.3389/fmed.2019.00250/full)

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The nature of salmonella is changing and it's meaner - MSUToday

Fifty-two faculty members and researchers at the University of California San Diego are among the worlds most influential in their fields. The Web of Science Group, an information and technology provider for the global scientific research community, compiled its2019 Highly Cited Researcherslist of more than 6,000 scientists from around the world whose studies were among the top 1% of most-cited publications in their field over the past 11 years.

The number of highly cited researchers from UC San Diego increased by 13% over last years number of forty-six. The listing covers 21 fields of study as well as a cross-field category for researchers who are widely cited across multiple fields. UC San Diego had researchers listed in 14 fields, with the most cited in cross-field (23), followed by molecular biology and genetics (5), clinical medicine (4) and social sciences (4).

UC San Diego has some of the most dedicated, brilliant and hard-working faculty and researchers in the world. Their inclusion on the list of highly cited researchers is a measure of their impact in their respective fields of study as they continue to advance the frontiers of knowledge, said Chancellor Pradeep K. Khosla.

Of particular note is Director for the Center of Microbiome Innovation Rob Knights inclusion in three separate areas of study (biology and biochemistry, environment and ecology, microbiology). Out of 6,216 highly cited researchers, only 11 were cited in three fields, making Knight part of a super elite 0.3% of those listed.

There were also 23 Nobel laureates on the list, one of whom, Roger Tsien, was a distinguished professor of both Pharmacology in the School of Medicine and of Chemistry and Biochemistry at UC San Diego until his death in 2016. He shared the Nobel Prize in Chemistry with two others in 2008 for discovering and developing green fluorescent protein.

David Pendlebury, Senior Citation Analyst at the Web of Science Groups Institute for Scientific Information said that the highly cited researchers create gains for society, innovation and knowledge that make the world healthier, richer, more sustainable and more secure.

It is especially encouraging to see not only the number of highly cited researchers at the university, but the broad range of fields in which they are cited. It really speaks to the fact that UC San Diego conducts groundbreaking research across a wide range of disciplines, said Vice Chancellor for Research Sandra A. Brown. I congratulate everyone on their excellent research and contributions.

The 52 UC San Diego faculty members named by Web of Science and the fields of study in which they were cited are:

Gregory Aarons,social sciences

Ludmil Alexandrov, molecular biology and genetics

David Brenner,cross-field

Kristin Cadenhead,psychiatry/psychology

Kelli Cain, social sciences

Shu Chien, cross-field

Don Cleveland,neuroscience and behavior

Seth Cohen,chemistry

Pieter Dorrestein,cross-field

Mark Ellisman, cross-field

Mark Estelle,plant and animal science

Michael Folger, cross-field

Anthony Gamst, cross-field

Christopher Glass,molecular biology and genetics

Uri Gneezy,economics and business

Antonio Gonzalez, microbiology

Kun-Liang Guan,molecular biology and genetics

Trey Ideker,cross-field

Michael Karin,molecular biology and genetics

Arthur Kavanaugh,clinical medicine

Dusan Keres, space science

Rob Knight,(listed in 3 fields) biology and biochemistry, environment and ecology, microbiology

Razelle Kurzrock, clinical medicine

Lisa Levin, cross-field

Irene Litvan, neuroscience and behavior

Rohit Loomba, clinical medicine

Prashant Mali, biology and biochemistry

Eliezer Masliah, cross-field

Victor Nizet, cross-field

Jerrold Olefsky,cross-field

Bernhard Palsson,biology and biochemistry

Veerabhadran Ramanathan,cross-field

Bing Ren,molecular biology and genetics

Jeremy Rich, cross-field

Douglas Richman,cross-field

Michael Sailor,cross-field

James Sallis,social sciences

William Sandborn,clinical medicine

Bernd Schnabl, cross-field

Julian Schroeder,plant and animal science

Terrence Sejnowski, cross-field

Claude Sirlin, cross-field

Murray Stein,psychiatry/psychology

Steffanie Strathdee, cross-field

Roger Tsien, cross-field

Ming Tsuang,psychiatry/psychology

Joseph Wang,chemistry

Shang-Ping Xie,geosciences

Gene Yeo, cross-field

Kun Zhang, cross-field

Liangfang Zhang,cross-field

Yunde Zhao, plant and animal science

Shu-Hong Zhu, social sciences

You can read about Web of Sciences methodology on their website.

UC San Diegos Studio Ten 300 offers radio and television connections for media interviews with our faculty. For more information, email .(JavaScript must be enabled to view this email address).

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52 UC San Diego Researchers Are Most Highly Cited in Their Fields - UC San Diego Health

A glance around the walls of Barry J. Byrnes office reveals a lot about the pediatric cardiologist who runs thePowell Gene Therapy Center at University of Florida (UF).

In one corner is an unusual painting by 9-year-old Will Barkowsky of Jacksonville, Fla. Will, the first boy with Duchenne muscular dystrophy to takeSarepta Therapeutics exon-skipping medication Exondys 51 (eteplirsen), put together his oil-on-canvas masterpiece using the tire tracks of his wheelchair, making sure the colors didnt mix.

Nearby is a movie poster for The Ataxian an award-winning 2015 documentary by Kevin Schlanser and Zack Bennett about 17-year-old Kyle Bryant, who despite having Friedreichs ataxia embarks on a cross-country bicycle trip with three buddies.

Another movie poster advertises Extraordinary Measures, the 2010 tearjerker starring Brendan Fraser as John Crowley the father of two kids with Pompe disease and later, the founder of Amicus Therapeutics and Harrison Ford as fictional researcher Robert Stonehill, who discovers a treatment for the genetic disorder that eventually saves the lives of Crowleys children.

Theres also a model of a Blalock-Taussig shunt frequently used in congenital heart surgery, as well as one of an adeno-associated virus (AAV) vector, along with a prominent photo of Byrne with Ron Bartek, co-founder and director of the Friedreichs Ataxia Research Alliance (FARA).

Friedreichs ataxia is where were putting most of our efforts now, said Byrne, who spoke to BioNews Services publisher of this website at length during a recent visit to his lab in Gainesville, Fla.

Byrne, along with Jerry Mendell, MD, a neurologist with Nationwide Childrens Hospital in Columbus, Ohio, hosted a Nov. 20 webinar on gene therapy organized by the National Organization for Rare Disorders (NORD) and the American Society for Gene & Cell Therapy.

The two experts were introduced by Katie Kowalski, senior program manager for NORDs Educational Initiatives. The webinar, Understanding the Gene Therapy Process and Aftercare, was the fourth in a five-part series underwritten by Amicus and Sarepta, as well as two other companies, Avrobio and Bluebird Bio.

The final webinar in the series, Life After Gene Therapy, is scheduled for Dec. 18.

Mendell, who heads Nationwides Center for Gene Therapy, specializes in gene therapy research for Duchenne as well as limb-girdle muscular dystrophy, spinal muscular atrophy (SMA) and X-linked myotubular myopathy. He was a principal investigator for the Novartis therapy Zolgensma, which uses an AAV vector to carry a working version of SMN1, the mutated gene in people with SMA.

Zolgensma won approval from the U.S. Food and Drug Administration (FDA) in May 2019 as the first gene therapy to treat SMA in infants up to 2 years of age.

At $2.125 million per patient, the hour-long Zolgensma infusion is the most expensive medicine in history. The cost easily eclipses that of the only other FDA-approved treatment for SMA, BiogensSpinraza(nusinersen), which retails for $750,000 the first year and $375,000 every year after.

Many of my colleagues have been trying to make inroads for years, Mendell said. When we first got into the gene therapy domain, we were limited by technology. We could not make enough virus for the kind of impact were having now. But technology has improved, and we can now deliver genes through circulation to reach all muscles.

Regardless of the disease, he said, its extremely important to confirm the patients specific mutation before anything else.

This is critical, because you dont want to deliver the wrong kind of gene in a disease like Friedreichs ataxia. That goes for all gene therapy trials, he said. Next, we want to check for pre-existing antibodies, whether theyre acquired from the environment or from close contact. They bind to the AAV and block entry to the target organ.

Checking for those antibodies requires a blood test. It generally takes 4-7 days to return lab results a nailbiting time for patients and families, Mendell said, because theyre waiting to be approved for enrollment in the trial.

Byrne estimated that 50-60% of all individuals may have been exposed to AAV.

Prior exposure at any level to any AAV infection is an exclusion in most studies, he said, noting that people who travel frequently or who have respiratory or gastrointestinal conditions are particularly susceptible. We are learning a lot about what thresholds are effective. Its about 10% of newborns and about 50% of those of school age and adulthood.

Patients must also be in general good health except, of course, for the genetic disease being treated. MRI and blood tests are done to rule out diabetes or any evidence of heart, liver, or kidney problems.

We put the patient to sleep so theres really no pain involved, Mendell said. We also use local numbing medicine, even though the patient is asleep, so theres no pain or discomfort.

The Powell Gene Therapy Center was established in 1996 the year before Byrne joined UF by Nicholas Muzyczka, PhD, who performed groundbreaking work on AAVs in the 1980s. The center has a dozen individual labs working in neuroscience and molecular genetics.

Byrne said that because gene therapy fundamentally changes many of the bodys cells, screening is crucial.

This is often a one-way street, in that since the effects are long-lasting, other experimental studies may not accept patients who have received gene therapy of any kind in the past, Byrne said. One must have the clinical features required of the study and meet certain functional and age criteria.

To prepare for screening, patients or their parents must read the informed consent and understand what the risks and benefits are. Genetic counseling also may be required to determine whether a given mutation is amenable to gene therapy.

Baseline evaluations are done when its a muscular skeletal disease timed function tests as well as lab tests and a study schedule is established, he said. In many of our studies, we see the patients very frequently, almost every day for the first two weeks. They stay in the area for up to a month. Because were often dealing with rare populations, that makes it convenient for us to evaluate these patients.

Byrne noted that gene therapy is not necessarily durable for the lifespan of the patient. Because the delivered gene does not integrate into the cells own DNA, it is not passed down to newly formed cells.

Some cells, particularly in the liver and muscle, continue to grow throughout childhood and AAV doesnt integrate, so its progressively less effective unless the cells being targeted, as in SMA, are not dividing, he said. Thats an example where newborn screening is critically important to better outcomes.

Mendell said he generally starts patients on prednisone one day before receiving gene therapy in order to suppress liver inflammation, and keeps them on it for 60 days after.

When were in the room, the first thing that happens is the gene is delivered. You push a button and get started, he said. Obviously it must be the correct gene. Its in there, but you cant see it.

The actual gene is delivered by intravenous (IV) infusion with a pump over a 90-minute period, Mendell said; anything faster than that could potentially cause harmful side effects.

We put IVs in both arms for continuous delivery in case one side gets clogged up. We dont want anything to stop gene delivery, he said. Meanwhile, the patient is constantly monitored for vital signs. We invite the whole family to stay together, and thats reassuring. Theres anxiety about gene therapy, but the potential benefits generally outweigh any risks involved.

Some patients may develop nausea and vomiting in the first one-to-three weeks following treatment. For this reason, blood is taken every two weeks for three months to check for side effects.

Mendell said he knows patients are responding to gene therapy by doing testing. In the case of Duchenne, he uses the North Star Ambulatory Assessment, which includes 17 timed tests such as climbing stairs, rising from a sitting position, and walking or running 100 meters. In addition, neck control is a very good indicator of efficacy among Duchenne boys, he said.

The FDA anticipates that within the next 10 years, it will approve up to 40 gene therapies for rare conditions. Mendell said the benefits of gene therapy for one condition in particular, SMA, are undeniable.

This is an absolutely devastating disease. In type 1 SMA, patients usually dont survive past age 2, and about 50% are gone by age 1, he said. Initially there was concern about giving this to infants, but we told the FDA we needed to test infants in order to save lives.

Continuing results from Mendells pivotal Phase 1 trial (NCT02122952) in 15 type 1 infants and along-term extension study (NCT03421977) have changed the way people view gene therapys potential in general.

After four years, he said, every patient in our trial went from being unable to sit to being able to, and several are able to walk. One patient was treated 28 days after birth, and now four years later, hes off to school. What Barry and I do is very gratifying, and we thank our patients and their families for this opportunity.

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Experts Barry Byrne, Jerry Mendell Lead NORD Webinar on Gene Therapy - Muscular Dystrophy News

On the left, a young dog (Jack), and on the right, an old dog (Snoop). Photo by Deborah Byrd.

What does it mean for us humans to age, and what does it mean for your dog to age? Turns out these two processes can be compared, some scientists are now saying, and we dont mean in the sense of the old adage that one dog year equals seven human years. That old saying has been recognized for some time as being, quite clearly, imprecise. If it were true, then like dogs humans should be able to reproduce at age 7. Many of us should live to be 150. Now, however, the tools of science have been applied to the question of true length of dog years. Biologist Tina Wang led new research at Ideker Lab at the UC San Diego School of Medicine. The work has resulted in a better formula for calculating your dogs age in human years. It stems from data on the effects of aging on dogs DNA. It takes breed size into account. The new formula suggests that a 1-year-old dog is closer to age 30 than age 7.

We humans and our dogs (and all other living things) have DNA within our cells, coded with the genetic information, inherited from generations of those who came before us. But aging isnt just about genetics. Its also about a healthy or unhealthy lifestyle, for example, and about whether you contract a disease. Scientists who study aging are now speaking of the effects of these environmental factors in terms of chemical markers on our DNA. These markers specifically methyl groups tag our DNA. According to a emerging theory of aging, its the changing pattern of these tags throughout our lives that determines whether you look and seem young for your age or instead age prematurely. This process the chemical modification of a persons DNA over a lifetime creates what aging researchers call an epigenetic clock

The researchers looked at DNA samples from 104 Labrador retrievers spanning a 16-year age range. They compared changes in their DNA samples against DNA previously collected from 320 humans between the ages of 1 and 103. They specifically looked for similarities in the methylation process between the two sets. Writing in the Washington Post on November 28, 2019, Christopher Ingraham explained that the researchers:

found that the DNA profiles evolved in similar ways across the life span of both [dogs and humans].

UCSDs Trey Ideker, leader of the lab that ran the study, told The Post:

If you look at the methylomes of 2-year-old Labs and you ask what are the closest human methylomes? The answer is that the best matches are in humans about 40 years old. That is just what the data show, no more, no less.

An example of the new dog aging chart using, for the sake of comparison, movie star Tom Hanks is below.

Read more via the Washington Post

EarthSky 2020 lunar calendars are available! They make great gifts. Order now. Going fast!

Wang, Ideker and colleagues illustrated their findings using 2 beloved icons: a Labrador and Tom Hanks. Heres the Washington Posts explanation of this chart: According to the DNA analysis, a 1-year-old Lab is equivalent to a Big-era Hanks, while a 4-year-old mirrors the actors star turn in The Da Vinci Code. By age 9, a Lab has obtained the approximate gravitas of Hanks starring as Ben Bradlee in The Post. Chart via Wang et al. and the Washington Post.

Want the actual formula for adjusting dogs ages to human years? You have to multiply the natural logarithm of the dogs age by 16 and add 31. Thus the formula is:

(human_age = 16ln(dog_age) + 31)

That looks like a complicated formula for most of us. Its the natural logarithm of the dogs real age, multiplied by 16, with 31 added to the total. This natural logarithm calculator might help.

Plus, youll find an easy-to-use dog age calculator in this article by Virginia Morell in Science on November 15, 2019.

Why study dog aging at all? As Morell points out in her article, its not just dogs and humans that undergo DNA methylation as they age. Mice, chimps and wolves have also been shown to have epigenetic clocks. Using dogs to study aging makes sense because dogs live in our homes, and many like their human owners receive once-a-year medical checkups and sometimes hospital treatments. Thus studying aging in dogs is another way of understanding how humans age.

Morell also spoke to Matt Kaeberlein, a biogerontologist at the University of Washington in Seattle, who was not involved with this research but whose lab is conducting a Dog Aging Project (open to all breeds) that includes epigenetic profiles of its canine subjects. He hopes to find out why some dogs develop disease at younger ages or die earlier than normal, whereas others live long, disease-free lives. Kaeberlein told Morell:

We already knew that dogs get the same diseases and functional declines of aging that humans do, and this work provides evidence that similar molecular changes are also occurring during aging.

Its a beautiful demonstration of the conserved features of the epigenetic age clocks shared by dogs and humans.

Read more via Science

Heres Jack again when he was 6 or 7 months old. He grew fast! According to the new formula devised by UC San Diego aging researchers, he would have been in his late teens or early 20s when this photo was taken.

Bottom line: A team of researchers on aging at the University of California San Diego performed a genetic analysis of dogs and humans and discovered that compared with humans dogs age faster at first. They reach the equivalent of human middle age after only a few years.

Source: Quantitative translation of dog-to-human aging by conserved remodeling of epigenetic networks

Via the Washington Post

Via Science

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A better way to convert dog years to human years - EarthSky

While robust market fundamentals point to a bright future for responsible aquaculture generally, in Norway massively improved biological material is paving the way for a rebound in cod farming in particular.

There has been very limited activity in cod production globally in recent years but that is about to change as pioneering aquaculture venture Norcod's plans to establish cod farming on an industrial scale gather momentum. Led by personnel with deep industry experience, Norcod is convinced that cod has the potential to be a significant contributor to the Norwegian economy. Quality biomass is the critical input factor.

Stemfish with poor biology and first-generation fry of inconsistent quality were partly to blame for the biomass loss seen during the last foray into cod farming between 2004 and 2012. Since then quantum leaps in biology have radically changed the landscape, with an estimated half-a-billion Norwegian kroner invested in two cod breeding programs that have been working quietly in the background in the belief that the tide would again turn.

Aquaculture-focused national research institute Nofima's breeding programme kicked off in 2002 with the goal to evolve economically important characteristics and disease resistance. Commercial hatchery player Havlandet Marin Yngel AS followed suit a year later. Their far-sighted commitment has seen the biological challenges of stagnant growth, susceptibility to infection and high escape figures systematically overcome.

Dramatically increased survival rate and quality of fry has been achieved through careful selection of eggs post fertilisation. The development of stemfish feed with minimal contamination has also boosted egg quality. Detailed comparative studies also showed that using eggs from four-year-old fish produce the best outcomes, according to Nofima.

Fish have been selected and developed for faster growth, higher harvest yield and higher resistance, while new feeds have been developed that support optimal growth and intestinal health. Farmed cod now grows up to 35 percent to 40 percent faster than fish in the wild.

Faster growth has always been the highest priority and has been the focus of the cod breeding programme. Breeding has led to a growth increase of 9 percent to 10 percent per generation, or around 3 percent per year about the same as for farmed salmon, says Atle Mortensen, senior scientist at Nofima.

Data from the stemfish produced for Norcod shows a dramatic 40 percent increase in survival rate for fish below 5 grams, up from 10 percent a decade ago. Successfully selecting for smaller heads has also been a game changer in boosting yield. In wild cod the much larger head can account for 40 percent of body weight.

Today's sixth generation of stem fish is a highly stable product and a completely different fish to 15 years ago, says Norcod managing director Rune Eriksen. Havlandet is now at capacity to deliver around three million fry, at 2-3 grams each, per annum. A kick-off batch of 260,000 fry from Nofima is already in production for Norcod and slated to go into the sea at the company's two facilities northwest of Trondheim imminently.

While growth was the holy grail, selecting specifically for other characteristics typically reduced the growth rate. Targeted breeding for disease resistance was unavoidable until the arrival of new and effective vaccines on the market. With these now available, the bacterial infections vibrosis and atypical furunculosis no longer pose a threat to farmed cod.

As per today there are no virus diseases that create problems for farmed cod. Both cod lice and sea lice affect cod but do not harm the fish like salmon lice do. Intestinal obstruction has very occasionally caused mortality in the sea phase. Compared to farmed salmon the health status of farmed cod is extremely good, says Mortensen.

The fish now show significant domestication, especially calm behaviour in the sea phase, swimming as a school in rings around the net much like salmon. That is astonishing given that selection was not made based on behaviour characteristics, says Mortensen. Not surprisingly, healthy, happy fish adapted to confinement grow faster. The high level of escape in the past was caused by the cod chewing holes in the nets. Today's tame fish display little desire to escape, while new standards and net technologies have also mitigated this tendency. Norcod's facilities are state of the art, optimising technical developments in equipment and feeding systems achieved in salmon farming in recent years.

Cannibalism is a peculiar trait of cod under stress but this problem has been virtually eradicated in the sixth generation of tame fish by means of improved feed and better feed distribution, allowing even growth across the population. Better growth, improved feed and optimal utilisation of feed also make it much easier to satisfy year-round demand.

Breeding has traditionally featured a combination of individual and family-based selection, with family selection ensuring diversity in the broodstock. The advent of molecular genetics, where information from the entire genome can be used for much greater precision in selecting for positive characteristics, promises even faster progress in the future.

Norcod stands to reap the rewards of these biological breakthroughs as a first mover. The quality of its cod is unmatched and unique globally. Initiating such a breeding project from scratch that could guarantee such strong characteristics would require a huge investment of time and money. But consumers want cod right now. Wild stocks are under pressure with limitations in capture quotas squeezing supply. Demand can only be met with cost-effective farming. Norcod's timing is on target to satisfy a market hungry for stable deliveries of fresh cod 12 months of the year.

Ensuring the welfare of the cod themselves throughout the production cycle also remains top priority. We should always remember that these are living creatures that should be handled with care and respect. No question, Eriksen says.

The production process from fry to plate takes between 23 to 26 months. Norcod has its sights set on sales of 9,000 tonnes of cod in 2021, rising to a total of 10 facilities with an output of 25,000 tonnes in 2025. We believe we have a very solid business case, says Eriksen. The market is waiting.

Read more from the original source:
Emerging science gives Norcod a path to further expansion - The Fish Site

Most of us on the University of Alberta campus have grown up intertwined with the internet. We are digital natives; social interaction on the web is just as natural as in-person communication to us. An essential part of our self-understanding as U of A students, then, comes not just from us interacting in physical space taking classes, participating in extracurriculars, and partying with our pals but also in the digital space of social media.

While the U of A has a plethora of social media pages dedicated to official campus organizations and events, there are a few private U of A pages that serve several purposes: asking questions about registration; sharing unique campus experiences; and even laughing at the U of A itself. How do all these pages operate differently, and how do they create a sense of identity on campus?

A block away from the Enbridge Centre, Im grabbing coffee with Ross Lockwood, the man who started one of the biggest U of A social media pages out there. Sitting at a table on a patio enclosed by office buildings, we sip coffee and talk about the origins of Overheard at the University of Alberta.

Overheard was started by Lockwood and a few friends back in 2007, back when Lockwood was in his third year of a physics degree and before Facebook allowed photo posts. Inspired by the blog Overheard in New York and the quote wall tradition in Lister, Lockwood says that the group mostly just wanted a fun space for U of A students to talk about the weird and wacky stuff theyd heard on campus.

[Overheard] was initially a small group, so maybe like five people had access to it, he says. But we made it public and more people found it useful its a good platform for discussions and things like that.

Due to its public status, the group began to grow very quickly. Overheard now has over 20,000 members, with posts being made daily. Overheard posts are supposed to tackle interesting, odd, or hilarious things overheard or seen on campus. Often this takes the form of text posts recalling snippets of conversation heard in a library; other times its bizarre photos of campus happenings.

If Overheard didnt exist, where would these people be expressing themselves, and where would that expression be appreciated?

Lockwood says that one of the reasons the group is great for U of A students is because it allows people to make connections that they may not have the chance to make in person. He cites Ray Dagg, a custodian at the University Station LRT stop, as one of the prime examples. Dagg, who has become a beloved figure in the group, often posts nature photos from around campus, which get a sizable amount of attention.

I think for a lot of people, being able to develop a community without face-to-face interaction is really good, he says. My question is, if Overheard didnt exist, where would these people be expressing themselves, and where would that expression be appreciated?

With the expansion of the group and Facebook adding new features over the years, the strictness of this doctrine has changed a bit. But its core philosophy has remained the same: make posts that are relevant to the U of A community.

Overheard has always [been about] whats relevant to the university community, Lockwood says. Memes might be funny for a subset of people, they might be annoying for another subset, but we really go for, does this contribute anything of value to the community at large?

This value is not just humorous or light-hearted anymore; at times, Overheard has been at the centre of more serious campus going-ons. One such event happened on October 21 2016, when multiple Overheard members began posting anecdotes about a man contemplating jumping off the sixth floor of CCIS (the man was later taken to hospital without injury). The incident, which was still ongoing when the first posts were made, sparked rampant discussion around the mans motivations, if he was safe, and how mental health is dealt with on campus. For Lockwood and the admin team at Overheard, this was a moment when they realized they needed to step up. They decided to include several campus and Edmonton mental health and distress line services on their page.

We were like, if its something that happens on campus and this person didnt have access to resources, we need to be the place where those resources exist, Lockwood says. Where else would somebody look for help? One of the first places that people get introduced to digitally [at] university, is Overheard.

A year before the CCIS incident, an Overheard post was made about Evan Tran, a U of A student who died by suicide. Tran was well-known on campus; he was a moderator on the Facebook page University of Alberta Compliments, volunteered with the Dean of Students office for their mental health initiatives, was a member of Students Council and General Faculties Council, and volunteered for various student groups. The post mentioning Tran has over 1,900 likes. Commenters are gave their condolences, offered solidarity with Trans family and other students on campus, and shared links to campus resources.

For Overheard admin and recent U of A engineering graduate Subhashis Chikoritaborty, this is one of his favorite moments hes seen on the page.

The amount of support I saw from faculty, [Trans] friends, and everyone who was close was absolutely incredible, he tells me.

Posts like these, and the reactions theyve garnered, seem to represent the other side of the discussion space that Overheard is attempting to foster: one thats not just about funny happenings, but also about vulnerable campus moments and the issues that affect all U of A students.

We want to create a discussion space where people should feel free to discuss [serious] things, [and] I think Overheard can provide that kind of space because its high-traffic, Chikoritaborty says. If you can share something like that [or] something vulnerable, we try to create a space where people can share those thoughts and feel a bit of comfort.

Moving on from Facebook, we come to reddit. More specifically, we come to r/uAlberta, the de-facto subreddit for the U of A community. Founded in 2011 and just over 13,500 members strong, the subreddit is a place for students to ask questions about anything related to their degree, including the quality of certain profs, how to register in certain courses, and what program is best to enroll in. Users have created lengthy guides for various programs and have told varied stories about their U of A experiences; some incredible successes, and some failures as well.

u/firesofpompeii, one of the admins of the subreddit and recent graduate from molecular genetics, says that the subreddit is set apart from other social media sites due to two things: its emphasis on anonymity, and its focus on user engagement.

With reddit in general, anyone can post at any time, [and] although there are users who are more well-known, its not like there are popular users who a lot of people follow, he says. [Everyone is] at an equal playing field, which you dont always get with other social media platforms.

The subreddit is not just a place to ask questions. Much like Overheard, r/ualberta has become a locus for campus discussion; unlike Overheard, however, the subreddits user anonymity has led to the rise and fall of several trollish characters.

If you were to sort of say something in a kind of normal way, often it doesnt get much traction on those sites, but if you say it in a more extreme way, you might get more of a reaction.

Theres been a few notorious users on the subreddit who have drawn the ire of many of the subreddits frequenters. The most notorious of them all, however, was u/unsunghero. They initially drew the ire of the subreddit by starting a thread called Am I too Competitive?. In the thread, they detailed how they would scout out classes considered GPA boosters and ask the professors to curve the class average down, all because they [wanted] to protect the sanctity of the A grade.

u/unsunghero would continue to troll the subreddit and share many controversial opinions, and soon the moderators of r/uAlberta were getting complaints. They couldnt do much, however, because u/unsunghero technically wasnt violating the rules of the subreddit. As long as a user is being civil in expressing their opinion, even if it is one that many people disagree with, the moderators let their posts stand.

Weve had a lot of users complain about them, thats why weve had to tell them that until theyre attacking other subscribers then theres nothing we can really do about it, u/firesofpompeii says. We definitely dont want to censor people.

To anyone whos spent anytime online, this kind of behaviour isnt unusual. Johnathan Cohn, an assistant professor in the department of English at the U of A whose research focuses on critical internet studies and digital culture, says that digital spaces often lend themselves to this kind of behaviour. This is both because theyre a relatively safe space to perform different identities and figure out who you are, and because these sites encourage more extreme modes of behaviour.

If you were to sort of say something in a kind of normal way, often it doesnt get much traction on those sites, but if you say it in a more extreme way, you might get more of a reaction, Cohn says. So it also sort of encourages people who are more extreme, in one way or another, to interact more, and it discourages people who maybe dont like that kind of interaction.

Trolls arent the only thing that the subreddit occasionally fosters. It has broken out into meme territory as well, creating lore that has arguably given the community its own identity and history beyond being a forum for student questions.

The most recent example of such territory is the Ghoul Wars, a saga that began on January 24 2019 with a post by u/lividnaynay that spoke of an experience they had with a particularly unhygienic student. Three days later, u/RogerMooreIsMyDad made a post stating I swear im (sic) going to buy a costco pack of deodorant and hand it out to all the little engg ghouls running around DICE.

That was enough to set off a dramatized war between the Ghouls and the Resistance. Posts were made detailing battle plans for the war, casualty reports, and the development of ghoul-repellant technology. Dozens upon dozens of these posts sprung up; it felt like an augmented reality game had suddenly began on the subreddit.

When I ask u/firesofpompeii about the Ghoul War, he simply laughs; I can practically hear his head shake over the phone.

That kinda made me feel really old, cause I had no idea what was going on, he says. I was just kind of a bystander to that.

In his five years as admin, this isnt the first time u/firesofpompeii has seen events like the Ghoul War arise. Back in 2016, r/uAlberta and r/UCalgary had a meme war, flaming each other in various memes over a period of a few months. Events like this are apparently cyclical on the subreddit; they come and go, cementing themselves as defining moments in the development of the rhetoric and identity of the subreddit.

With each of these cycles, r/uAlberta slowly becomes its own community apart from the physical U of A.

The term meme was first coined by Richard Dawkins in his book The Selfish Gene. For Dawkins, memes are like genes of culture; they are ideas and concepts that spread in communities and get passed down over time. A memes fidelity how well it can retain its original idea as it spreads varies depending on the specificity of the idea. Oftentimes memes with community-specific ideas dont travel very far, whiles memes with more generalizable ideas do.

This can be seen in the different content U of A-related Instagram meme pages put out. Some pages like @ualberta_memes stick very close to U of A material, with past topics including Konz (a short-lived and universally hated pizza place in the Students Union Building), the UASU, and other U of A happenings. Other pages, like @uofaenggmemes seem to take general engineering student memes and put a U of A label on them.

[More generalized memes] translate very broadly but are very weak in their transmission, Cohn says. They can be rethought and reused in a lot of ways, but the original meaning or community [from whence the meme came] gets lost very quickly.

@ualberta_memes is the biggest U of A Instagram meme page, having gained over 6,600 followers since its start on February 4 2019. The admin of the page a third-year kinesiology student who wishes to remain anonymous tells me over the phone that he started the page as a way to kill boredom. He posted a few memes on that fateful day, and the response he received encouraged him to continue.

We can either come to school and just clock-in clock-out, or you can look at everything around you and kind of care a little more than you usually do.

@ualberta_memes sources his content from a variety of places. Typically he makes the memes himself and posts them directly to his page, but he also will post submissions and take ideas for memes. The core of his content, in typical internet meme fashion, pokes fun at a group; namely, the various faculties on campus.

A lot of it is just to show that we all have faults and we can all kind of make fun of ourselves to a certain level, he says.

@ualberta_memes feels personally that the U of A lacks a strong sense of culture, given how large the school is and that people from all over the world attend it. Through making posts that highlight universal U of A experiences like the disaster that was Konz or Listers dodgeball culture @ualberta_memes hopes to help students feel more connected to their campus.

You get people [starting] to care a little more about the small things that you see on campus, he says. Thats kind of important because we can either come to school and just clock-in clock-out, or you can look at everything around you and kind of care a little more than you usually do.

In this way, students are able to feel more attached to their campus and to each other in more tangible ways; instead of simply proclaiming Im a U of A student because I go to the U of A, students can begin to point out the multitude of small, specific details that make up their campus experience.

Another account, @ualbertameme, started just a month after @ualberta_memes. The main admin of the page a third-year science student who also wished to remain anonymous was inspired to start his page in a similar way to @ualberta_memes.

When sourcing posts for the page, @ualbertameme looks for universal U of A experiences that are easily translatable into memes. The page is run by a small team of about five people, all of whom work on different aspects of the page; some post content, others check analytics, and others handle responding to DMs and comments from followers.

Some of the feedback that @ualbertameme has gotten from his followers is that his pages memes help boost student morale, especially during exam season. In a way, being able to laugh about the experience of being a U of A student helps to bring people together and make student life a little easier.

University is supposed to be a relatively fun experience, although it can get really difficult at times, he says. I guess seeing things like memes kind of helps alleviate the pressure or the anxiety that comes with university.

What makes an Instagram meme page different from hanging out on Overheard or r/uAlberta? Both page admins have different answers. For @ualberta_memes, its having an anonymous admin post all the memes. He can post memes on behalf of people who are afraid of judgement, and can also act as a scapegoat in case someone gets upset about their faculty being made fun of.

The whole anonymous aspect of me posting, I think, gives people more comfort to comment what they want, he says. It doesnt have to feel like whoever is posting it might be made fun of or might be judged by their friends or something.

Its easy on these sites to feel like you have nothing to contribute and that therefore youre not part of the community, but thats the normal situation.

For @ualbertameme, its the relaxed nature of Instagram pages, which dont have to have as strict of accountability measures as other platforms.

Certain pages like Overheard, they have to appear [to have] a certain level of responsibility and accountability, he says. On meme pages, people can post whatever they want and there wouldnt really be any repercussions unless its a very serious thing.

***

If theres one thing all of these pages try to do, its capture fragments of the U of A student experience and provide a space for them to be disseminated and discussed. With their varying degrees of anonymity, subject matter, and unique rhetoric and rules, each page fills a different niche.

Many of us may feel out of place on these pages; we may lurk instead of post, feeling out of place or feeling like we lack something to contribute. But as Cohn said before, most people who post on these pages are on the hyper end of extroverted, and they likely only make up a small percentage of the group.

If youre someone in these groups who doesnt post much and you feel sort of marginal, you are actually the norm, he says. Its easy on these sites to feel like you have nothing to contribute and that therefore youre not part of the community, but thats the normal situation.

Lurker or poster, we all can feel more connected to our campus through these pages. They bring us together in times of need, alleviate exam pain, foster discussion about issues on campus, and help us begin to love the little things about being a U of A student.

These pages, arguably, are just as integral to being a U of A student as going to class.

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Student life through the screen - The Gateway Online

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Some of the same mutations allowing humans to fend off deadly infections also make us more prone to certain inflammatory and autoimmune diseases, such as Crohn's disease. In a review published November 27 in the journalTrends in Immunology, researchers describe how ancestral origins impact the likelihood that people of African or Eurasian descent might develop immune-related diseases. The authors also share evidence that the human immune system is still evolving depending on a person's location or lifestyle.

"In the past, people's lifespans were much shorter, so some of these inflammatory and autoimmune diseases that can appear in the second half of life were not so relevant," says first author Jorge Dominguez-Andres (@dominjor), a postdoctoral researcher at Radboud Institute for Molecular Life Science in the Netherlands. "Now that we live so much longer, we can see the consequences of infections that happened to our ancestors."

One of the body's best defenses against infectious diseases is inflammation. Dominguez-Andres and senior author Mihai Netea, a Radboud University immunologist and evolutionary biologist, compiled data from genetics, immunology, microbiology, and virology studies and identified how the DNA from people within different communities commonly infected with bacterial or viral diseases was altered, subsequently allowing for inflammation. While these changes made it more difficult for certain pathogens to infect these communities, they were also associated with the emergenceover timeof new inflammatory diseases such as Crohn's disease, Lupus, and inflammatory bowel disease.

"There seems to be a balance. Humans evolve to build defenses against diseases, but we are not able to stop disease from happening, so the benefit we obtain on one hand also makes us more sensitive to new diseases on the other hand," says Dominguez-Andres. "Today, we are suffering or benefiting from defenses built into our DNA by our ancestors' immune systems fighting off infections or growing accustomed to new lifestyles."

For example, the malaria parasite Plasmodium sp. has infected African populations for millions of years. Because of this, evolutionary processes have selected people with DNA that favors resistance to infections by causing more inflammation in the body. In doing so, this has also contributed to making modern Africans prone to developing cardiovascular diseases, such as atherosclerosis, later in life.

Dominguez-Andres and Netea also write about how the early-human ancestors of Eurasians lived in regions still inhabited by Neanderthals and interbred. Today, people with remainders of Neanderthal DNA can be more resistant against HIV-1 and 'staph' infections, but are also more likely to develop allergies, asthma, and hay fever.

The negative side effects of changes in each population's immune systems are a relatively recent finding. "We know a few things about what is happening at the genetic level in our ancestry, but we need more powerful technology. So, next generation sequencing is bursting now and allowing us to study the interplay between DNA and host responses at much deeper levels," says Dominguez-Andres. "So, we are obtaining a much more comprehensive point of view."

These technologies are also revealing how our immune systems are evolving in real time because of modern lifestyle changes. African tribes that still engage in hunting have greater bacterial gut diversity than urbanized African-Americans that eat store-bought foods. Also, changes in hygiene patterns seen in the last two centuries have improved sanitation, drinking water, and garbage collection, and have led to reduced exposure to infectious pathogens relative to previous times. As humans move toward processed foods and stricter hygiene standards, their bodies adapt by developing what researchers call "diseases of civilization," such as type 2 diabetes.

Moving forward, Dominguez-Andres and Netea will expand their research to communities that fall outside African and Eurasian populations. "So far, all of the studies we went through are focused on populations with European and African descent, but they must also be extended to indigenous and other populations to improve the representation of human genetic diversity," says Dominguez-Andres. "Lifestyles and ecologic natures can really differ and influence immune responses. So, more work needs to be done."

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Humans Co-Evolved with Immune-Related Diseasesand It's Still Happening - Lab Manager Magazine

A thousand seemingly insignificant things change as an organism ages. Beyond the obvious signs like graying hair and memory problems are myriad shifts both subtler andmore consequential: Metabolic processes run less smoothly; neurons respond less swiftly; the replication of DNA grows faultier.

But while bodies mayseem to just gradually wear out, many researchers believe instead that aging is controlled at the cellular and biochemical level. They find evidence for this in the throngof biological mechanisms that are linked to aging but also conserved across species as distantly related as roundworms and humans. Whole subfields of research have grown up around biologists attempts to understand the relationships among the core genes involved in aging, which seem to connect highly disparate biological functions, like metabolism and perception. If scientists can pinpoint which of the changes in these processes induce aging, rather than result from it, it may be possible to intervene and extend the human life span.

So far, research has suggested that severely limiting calorie intake can have a beneficial effect, as can manipulating certain genes in laboratory animals. But recently in Nature, Bruce Yankner, a professor of genetics and neurology at Harvard Medical School, and his colleagues reported on a previously overlooked controller of life span: the activity level of neurons in the brain. In a series of experiments on roundworms, mice and human brain tissue, they found that a protein called REST, which controls the expression of many genes related to neural firing, also controls life span. They also showed that boosting the levels of the equivalent of REST in worms lengthens their lives by making their neurons fire more quietly and with more control. How exactly overexcitation of neurons might shorten life span remains to be seen, but the effect is real and its discovery suggests new avenues for understanding the aging process.

In the early days of the molecular study of aging, many people were skeptical that it was even worth looking into. Cynthia Kenyon, a pioneering researcher in this area at the University of California, San Francisco, has described attitudes in the late 1980s: The ageing field at the time was considered a backwater by many molecular biologists, and the students were not interested, or were even repelled by the idea. Many of my faculty colleagues felt the same way. One told me that I would fall off the edge of the Earth if I studied ageing.

That was because many scientists thought that aging (more specifically, growing old) must be a fairly boring, passive process at the molecular level nothing more than the natural result of things wearing out. Evolutionary biologists argued that aging could not be regulated by any complex or evolved mechanism because it occurs after the age of reproduction, when natural selection no longer has a chance to act. However, Kenyon and a handful of colleagues thought that if the processes involved in aging were connected to processes that acted earlier in an organisms lifetime, the real story might be more interesting than people realized. Through careful, often poorly funded work on Caenorhabditis elegans, the laboratory roundworm, they laid the groundwork for what is now a bustling field.

A key early finding was that the inactivation of a gene called daf-2 was fundamental to extending the life span of the worms. daf-2 mutants were the most amazing things I had ever seen. They were active and healthy and they lived more than twice as long as normal, Kenyon wrote in a reflection on these experiments. It seemed magical but also a little creepy: they should have been dead, but there they were, moving around.

This gene and a second one called daf-16 are both involved in producing these effects in worms. And as scientists came to understand the genes activities, it became increasingly clear that aging is not separate from the processes that control an organisms development before the age of sexual maturity; it makes use of the same biochemical machinery. These genes are important in early life, helping the worms to resist stressful conditions during their youth. As the worms age, modulation of daf-2 and daf-16 then influences their health and longevity.

These startling results helped draw attention to the field, and over the next two decades many other discoveries illuminated a mysterious network of signal transduction pathways where one protein binds another protein, which activates another, which switches off another and so on that, if disturbed, can fundamentally alter life span. By 1997, researchers had discovered that in worms daf-2 is part of a family of receptors that send signals triggered by insulin, the hormone that controls blood sugar, and the structurally similar hormone IGF-1, insulin-like growth factor 1; daf-16 was farther down that same chain. Tracing the equivalent pathway in mammals, scientists found that it led to a protein called FoxO, which binds to the DNA in the nucleus, turning a shadowy army of genes on and off.

That it all comes down to the regulation of genes is perhaps not surprising, but it suggests that the processes that control aging and life span are vastly complex, acting on many systems at once in ways that may be hard to pick apart. But sometimes, its possible to shine a little light on whats happening, as in the Yankner groups new paper.

Figuring out which genes are turned on and off in aging brains has long been one of Yankners interests. About 15 years ago, in a paper published in Nature, he and his colleagues looked at gene expression data from donated human brains to see how it changes over a lifetime. Some years later, they realized that many of the changes theyd seen were caused by a protein called REST. REST, which turns genes off, was mainly known for its role in the development of the fetal brain: It represses neuronal genes until the young brain is ready for them to be expressed.

But thats not the only time its active. We discovered in 2014 that [the REST gene] is actually reactivated in the aging brain, Yankner said.

To understand how the REST protein does its job, imagine that the network of neurons in the brain is engaged in something like the party game Telephone. Each neuron is covered with proteins and molecular channels that enable it to fire and pass messages. When one neuron fires, it releases a flood of neurotransmitters that excite or inhibit the firing of the next neuron down the line. REST inhibits the production of some of the proteins and channels involved in this process, reining in the excitation.

In their new study, Yankner and his colleagues report that the brains of long-lived humans have unusually low levels of proteins involved in excitation, at least in comparison with the brains of people who died much younger. This finding suggests that the exceptionally old people probably had less neural firing. To investigate this association in more detail, Yankners team turned to C. elegans. They compared neural activity in the splendidly long-lived daf-2 mutants with that of normal worms and saw that firing levels in the daf-2 animals were indeed very different.

They were almost silent. They had very low neural activity compared to normal worms, Yankner said, noting that neural activity usually increases with age in worms. This was very interesting, and sort of parallels the gene expression pattern we saw in the extremely old humans.

When the researchers gave normal roundworms drugs that suppressed excitation, it extended their life spans. Genetic manipulation that suppressed inhibition the process that keeps neurons from firing did the reverse. Several other experiments using different methods confirmed their results. The firing itself was somehow controlling life span and in this case, less firing meant more longevity.

Because REST was plentiful in the brains of long-lived people, the researchers wondered if lab animals without REST would have more neural firing and shorter lives. Sure enough, they found that the brains of elderly mice in which the Rest gene had been knocked out were a mess of overexcited neurons, with a tendency toward bursts of activity resembling seizures. Worms with boosted levels of their version of REST (proteins named SPR-3 and SPR-4) had more controlled neural activity and lived longer. But daf-2 mutant worms deprived of REST were stripped of their longevity.

It suggests that there is a conserved mechanism from worms to [humans], Yankner said. You have this master transcription factor that keeps the brain at what we call a homeostatic or equilibrium level it doesnt let it get too excitable and that prolongs life span. When that gets out of whack, its deleterious physiologically.

Whats more, Yankner and his colleagues found that in worms the life extension effect depended on a very familiar bit of DNA: daf-16. This meant that RESTs trail had led the researchers back to that highly important aging pathway, as well as the insulin/IGF-1 system. That really puts the REST transcription factor somehow squarely into this insulin signaling cascade, said Thomas Flatt, an evolutionary biologist at the University of Fribourg who studies aging and the immune system. REST appears to be yet another way of feeding the basic molecular activities of the body into the metabolic pathway.

Neural activity has been implicated in life span before, notes Joy Alcedo, a molecular geneticist at Wayne State University who studies the connections between sensory neurons, aging and developmental processes. Previous studies have found that manipulating the activity of even single neurons in C. elegans can extend or shorten life span. Its not yet clear why, but one possibility is that the way the worms respond biochemically to their environment may somehow trip a switch in their hormonal signaling that affects how long they live.

The new study, however, suggests something broader: that overactivity in general is unhealthy. Neuronal overactivity may not feel like anything in particular from the viewpoint of the worm, mouse or human, unless it gets bad enough to provoke seizures. But perhaps over time it may damage neurons.

The new work also ties into the idea that aging may fundamentally involve a loss of biological stability, Flatt said. A lot of things in aging and life span somehow have to do with homeostasis. Things are being maintained in a proper balance, if you will. Theres a growing consensus in aging research that what we perceive as the body slowing down may in fact be a failure to preserve various equilibria. Flatt has found that aging flies show higher levels of immune-related molecules, and that this rise contributes to their deaths. Keeping the levels in check, closer to what they might have been when the flies were younger, extends their lives.

The results may help explain the observation that some drugs used for epilepsy extend life span in lab animals, said Nektarios Tavernarakis, a molecular biologist at the University of Crete who wrote a commentary that accompanied Yankners recent paper. If overexcitation shortens life span, then medicines that systematically reduce excitation could have the opposite effect. This new study provides a mechanism, he said.

In 2014, Yankners laboratory also reported that patients with neurodegenerative diseases like Alzheimers have lower levels of REST. The early stages of Alzheimers, Yankner notes, involve an increase in neural firing in the hippocampus, a part of the brain that deals with memory. He and his colleagues wonder whether the lack of REST contributes to the development of these diseases; they are now searching for potential drugs that boost REST levels to test in lab organisms and eventually patients.

In the meantime, however, its not clear that people can do anything to put the new findings about REST to work in extending their longevity. According to Yankner, REST levels in the brain havent been tied to any particular moods or states of intellectual activity. It would be a misconception, he explained by email, to correlate amount of thinking with life span. And while he notes that there is evidence that meditation and yoga can have a variety of beneficial effects for mental and physical health, no studies show that they have any bearing on REST levels.

Why exactly do overexcited neurons lead to death? Thats still a mystery. The answer probably lies somewhere downstream of the DAF-16 protein and FoxO, in the genes they turn on and off. They may be increasing the organisms ability to deal with stress, reworking its energy production to be more efficient, shifting its metabolism into another gear, or performing any number of other changes that together add up a sturdier and longer-lived organism. It is intriguing that something as transient as the activity state of a neural circuit could have such a major physiological influence on something as protean as life span, Yankner said.

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Longevity Linked to Proteins That Calm Overexcited Neurons - Quanta Magazine

Spitting intotheplastic test tube, I felt nervous. I was offering up a piece of myself for decoding, and while this timethere was no silver-haired sage, it reminded me of a visit to a fortune teller when I was 21.

Then, I offeredthepalm of my hand in a bid to divine what fate had planned for me. Now, it wasDNA, with my saliva destined for a laboratory in southwest China, totheheadquarters ofChengdu 23Mofang Biotechnology Co., a startup thats seeking to tap a boom in consumer genetics intheworlds most populous nation.

Rising awareness of genetically-linked diseases like Alzheimers and a natural human curiosity for insight intothefuture is fueling a global market for direct-to-consumerDNAtesting thats predicted totripleoverthenext six years. In China, wherethegovernment has embraced genetics as part of its push to become a scientific superpower,theindustry is expected to see US$405 million in sales by 2022, according to Beijing research firm EO Intelligence, an eight-fold increase from 2018. Some 4 million people will send away test tubes of spit in China this year, and I had just become one ofthem.

Not only was I entering a world where lack of regulation has spawned an entire industry devoted to identifyingthefuture talents of newborn babiesthroughtheir genes, I was handing over my genetic code to a country wherethegovernment has been accused of usingDNAtesting to profile minority groups a concern that hit home whentheresults showed I was a member of one.

I wanted to see whethertheburgeoning industry delivered on its claims in China, where scientists have gained international attention and criticism for pushingtheboundaries of genetics. And as a child of Vietnamese immigrants totheUS, Ive long been curious about my ancestry and genetic makeup.

To get an idea of how this phenomenon is playing out intheworlds two biggest consumer markets, I comparedtheDNAtesting experience of 23Mofang withthefirm CEO Zhou Kun says it was inspired by:23andMe Inc., one ofthebest known consumer genetics outfits intheUS.

PushingtheEnvelope

Thedifferences betweenthetwo companies are stark.

23andMe was co-founded byAnne Wojcicki, a Wall Street biotech analyst once married toGoogleco-founderSergey Brin.TheMountain View, California-based firm has more than 10 million customers and has collected 1 billion genetic data points, according to itswebsite. Brin and Google were early investors.

By contrast, 23Mofang is run out oftheChinese city of Chengdu, and Zhou, 36, is a computer science graduate who createdthecompany after becoming convinced Chinas next boom would be inthelife sciences sector. 23Mofang expects to have 700,000 customers bytheend of this year, a number he projects will at least double in 2020.

Thedivergence betweenthetwo countries andtheir regulation oftheindustry is just as palpable. Chinas race to dominate genetics has seen it push ethical envelopes, with scientistHe Jiankuisparking a global outcry last year by claiming to have editedthegenes of twin baby girls.Theexperiment, which He said madethem immune to HIV, put a spotlight on Chinas laissez-faire approach to regulating genetic science andthebusinesses that have sprung up around it.

When my reports came back, 23Mofangs analysis was much more ambitious than its American peer. Its results gauged how long I will live, diagnosed a high propensity for saggy skin (recommending I use products including Olay and Estee Lauder creams) and gave me an optimist not prone to mood swings a higher-than-average risk of developing bipolar disorder. 23andMe doesnt assess mental illness, which Gil McVean, a geneticist at Oxford University, says is highly influenced by both environmental and genetic factors.

Thefortune teller who pored over my palm told me I would live to be a very old woman. 23Mofang initially said I had a better-than-average chance of living to 95, before revisingtheresults to say 58% of clients hadthesame results as I did, making me not that special, and perhaps not that long-living.

When I ranthefinding pastEric Topol, a geneticist who foundedtheScripps Research Translational Institute in La Jolla, California, he laughed. Ninety-five years old?Theres no way to put a number on longevity, he said. Its a gimmick. Its so ridiculous.

Zhou saidtheaccuracy ofthelongevity analysis, based on a 2014 genetics paper, is not too bad, thoughthecompany plans to updatetheanalysis with research thats being undertaken on Chinese elderly.

But when it comes to disease,theresults of both companies showed howthescience of genetics, particularly attheconsumer level, is still a moving target.

Its All AbouttheData

After claiming I had a 48% greater risk thanthegeneral population of developing type 2 diabetes, both 23Mofang and 23andMethen revisedtheresults.

First, 23andMe cuttherisk figure from its analysis, posted in an online portal I accessed with a password.Theoverview analysis that I have an increased likelihood of developingthedisease never changed. But a few months later,thefigure was back, with a slightly different explanation: Based on data from 23andMe research participants, people of European descent with genetics like yourshave an estimated 48% chance of developing type 2 diabetes at some point between your current age and 80.

Shirley Wu, 23andMes director of health product, saidthecompany occasionally updates its analysis. My risk figure might have changed if I indicated my ethnicity and age, she said. I hadnt given any biographical details or filled out any surveys on 23andMes site.

Your risk estimates will likely change over time as science gets better and as we have more data, Wu said. We are layering in different non-genetic risk factors, and that potentially updates our estimates.

Algorithms and data underpintheanalysis of both companies, asthey do for other genetic testing firms, so it apparently isnt unusual forDNAanalysis to shift as more research and data into diseases becomeavailable. Still, I was confused.

I reached out to Topol, who said that 23andMes diabetes finding likely didnt apply to me sincethevast majority of people studied forthedisease are of European descent. Wu saidthe American company does have a predominantly European database but has increased efforts to gather data for other ethnicities as well.

23Mofang, meanwhile, also revised my diabetes risk to 26%. My genes hadnt changed, so why hadtheresults? CEO Zhou saidthecompany is constantly updating its research and datasets, and that may changetheanalysis. As time goes by,there will be fewer corrections and greater accuracy, he said.

For now, theres a possibility you can later get a result thats opposite oftheinitial analysis, said Zhou.

Additionally,theaccuracy of genetic analysis varies hugelydepending onthetraits and conditions tested because some are less genetically linkedthan others.

Zhou isnt deterred by criticism. He said 23Mofang employs big data and artificial intelligence to findthecorrelations to diseases without relying on scientists to figure it out.

While its impossible to get things 100% right,thecompanys accuracy will get better with more data, he said.

Ancestry Mystery

You might assume thatthetwo companies would offer similar analysis of my ancestry, which Ive long thought to be three-fourths Vietnamese and one-fourth Chinese (my paternal grandfather migrated from China as a young man). Born in Vietnam and raised intheUS, I now live in Hong Kong, a special administrative region of China.

23andMes analysis mirrored what I knew, but my ancestry according to 23Mofang? 63% Han Chinese, 22% Dai an ethnic group in southwestern China and 3% Uyghur. (It didnt pick up my Vietnam ancestry becausetheanalysis only compares my genetics to those of other Chinese, according tothecompany.)

That led me tothebig question in this grand experiment: How safe is my data afterthesetests?

Human Rights Watch said in 2017 that Chinese authorities collectedDNAsamples from millions of people in Xinjiang,thepredominately Muslim region thats home totheUyghur ethnic group. Chinas use of mass detention and surveillance intheregion has drawn international condemnation. What if Beijing compelled companies to relinquishdata on all clients with Uyghur ancestry? Couldthedetails of my Uyghur heritage fall into government hands and put me at risk of discrimination or extra scrutiny on visits to China?

23Mofangs response tothese questions didnt give me much solace. Regulations enacted in July gavethegovernment access to data held by genetics companies for national security, public health and social interest reasons.Thecompany respectsthelaw, said Zhou. Ifthelaw permitsthegovernments access tothedata, we will give it, he said.

Theauthorities havent made any requests for customer data yet, Zhou pointed out. Chinas State Council, which issuedtheregulations, andtheMinistry of Science & Technology didnt respond to requests for comment.

Over intheUS, 23andMe said it never shares customer data with law enforcement unlesstheres a legally valid requestsuch as a search warrant or written court order.Thecompany said its had seven government requests for data on 10 individual accounts since 2015 and has not turned over any individual customer data. It uses all legal measures to challenge such requests to protect customers privacy, said spokeswoman Christine Pai.

No Protection

New York Universitybioethics professorArt Caplansays privacy protections on genetic information are poor in most countries, including in the USand China.

I dont think anyone can say theyre going to protect you, he said. In China, its even easier for the government. The government retains the right to look.

23andMe appeals to potential customers with the lure of being able to make more informed decisions about your health, but after taking tests on both sides of the Pacific and realizing how malleable the data can be, as well as the myriad factors that determine diseases and conditions, I am left more skeptical than enlightened.

I gave away something more valuable than a vial of spit the keys to my identity. It could become a powerful tool in understanding disease and developing new medicines, but in the end its entrepreneurs like Zhou who will ultimately decide what to do with my genetic data. He plans to eventually look for commercial uses, like working with pharmaceutical companies to develop medicines for specific diseases.

We want to leverage the big database we are putting together on Chinese people, Zhou said. But first, we need to figure out how to do it ethically.

Read this article:
How do consumer DNA tests from the US and China stack up? - Abacus

I mightve died fearing the ageing process about as much as everyone else. Unfortunately, about two drags into my fourth cigarette a friend of mine relayed an anecdote about his dying grandfatherunprompted.

So its his ninety-eighth birthday and were watching him try to blow out candles on a cake he probably cant eat anywayfor like an hour.Eventually, I get bored and blow it out for him before asking what he wished for. To which he says: I accidentally peeped the expiration date on the carton of milk in the fridge and it dawned on me that I didnt know which one of us had more time left.

In an instant, I quit smoking and took up gerascophobia. In defense of the soon-to-be-dead-party-pooper, the older we get the louder minute hands become. We try to dull the racket by route of cosmetics, pop culture, copulation and fairy-tales; all to distract ourselves from the inevitable frog march into nothingness. If were honest, every year after 50 extends a catalog of things we cant do anymore. The list begins innocuously enough with things like fit into my favorite pair of whatevers or comprehend the cultural significance of this or that, but then the whole thing ends tragically nuanced.

Were all familiar with the odd way time seems to speed up every year after 21? It makes sense that time adopts the illusion of expedience as we run out of milestones but the reasoning behind this phenomenon is actually even less abstract than that. According to a new paper published in the scientific journalEuropean Review, as wrinkles begin to appear, and our postures sag, our neurons grow larger, increasing the amount of time it takes us to process an image.

People are often amazed at how much they remember from days that seemed to last forever in their youth, explained the new studys author Adrian Bejan, the J.A. Jones Professor of Mechanical Engineering at Duke University in a pressrelease.Its not that their experiences were much deeper or more meaningful, its just that they were being processed in rapid-fire.

Interestingly enough, almost all of the psychological conditions that narrate our morph into maggot food are effected by well-documented physiological precursors.

Little mutations join forces to pen an aggressive eviction notice apostrophized by medical abnormalities that condemn life on planet earth to be less and less pleasant.This is especially relevant right now because Americas global age is increasing at an exponential rate.

When a society attains economic and agricultural excellence the death rate decreases alongside birthrate, which leads to a larger and older population.James Fries, professor of medicine at Stanford University, indexed the sociological fine-print that punctures this developmental achievement back in 1998. What Fries calls the compression of morbidity dictates that denizens of a thriving nation enjoy healthy lives for most of it until a series of health setbacks plague them all at once toward the final stretch. This is often in the form of chronic illness that appears in tandem with natural biological regressions. As far as the perversion of our mind clocks are concerned, organic changes in saccades frequency, body size, and pathway degradation have been studied to be the primary culprits. This is what physics more discreetly refers to asthe constructional law of low architecture. Elderly people simply receive fewer images in the same amount of time as younger people, drastically decelerating their integration of information. The mechanisms that animate this process are fairly identical to a cameras shutter speed.

The human mind senses time changing when the perceived images change, Bejan adds. The present is different from the past because the mental viewing has changed, not because somebodys clock rings. Daysseemed to last longerin your youth because the young mind receives more images during one day than the same mind in old age.

Overall somatic decline is ensured by similar physiological defects. New data published by researchers at Yale University revealed that our ability to obtain energy by burning belly fat also reduces as we grow older. This impairment is a direct cost of medical and agricultural preferments that have allowed us to defy our intended life expectancy.

Several mechanisms in the body are not selected for longevity,explained the papers lead researcher, Vishwa Deep Dixit. Normally the B cells produce antibodies and defend against infection. But with aging, the increased adipose B cells become dysfunctional, contributing to metabolic disease. This predisposes an animal to diabetes and metabolic dysfunction like inability toburn fat.

Thankfully, successful aging is no longer a consideration beholden to science fiction. Genetics may draft the treatment, but our lifestyle choices govern how gracefully we interpret the consequential beats. Presbycusis for instance (gradual degeneration of the cochlea consequenced by bilateral symmetrical aging) is by all accounts unavoidable. It is the leading cause of hearing loss and affects just about one and two individuals over the age of 75. However, there are cumulative environmental predictors that can worsen the condition and even accelerate its development. Prolonged exposure to headphone frequencies causes the hair cells in the cochlea to bend beyond the point of repair. Uniformly, we all have a reserve capacity of cells, each of which dies without fanfare throughout a given day.

Of course, as we age, this process, which is calledapoptosis, picks up momentum. What you might not know though is our state of mind mandates how quickly and violently this program transpires.

Having a good attitude is very important. We know that stress plays a key role in how we will age. We have these hormones, these stress hormones, that actually play a role in how our cells will die. When we become under stress we have an accelerated loss of cells. So this over a lifetime plays a major role in how functional we will be, explainedSteven Gambert, MD.

Even more consistently than this is the role our diet plays in the pace of our weathering. Diets like the Mediterranean, a regimen rich in vegetables and olive oil, low in meat ingestion, and moderate in alcohol consumption, slackens the agents of aging by checking their pawns, namely chronic maladies associated with old age. A recent study conducted on 23,349 men and women confirmed what previous literature had intimated in years prior. Medical journalist, Caroline Wilbert reports:

During the study period, there were 652 deaths among 12,694 participants who had lower Mediterranean diet scores of 0-4 and 423 deaths among the 10,655 participants who had higher scores of at least 5. In general, those with higher scores were more likely to still be alive at the end of the study.

Similarly, earlier this year a team of European researchers disclosed that routine coffee consumption contributes to DNA integrity and overall longevity. This is earned by the antioxidants residing in dark roasted beans, a compound that helps cells repair themselves more effectively in the wake of the damage done by free radicals. Free radicals, birthed by sunlight, oxygen, and pollution, deteriorate the collagen fibers in the skin. The microbial properties in coffee help staff off these very same germs. Its caffeine acid boosts collagen levels which in turn brakes the aging process.

When it comes to confronting the aspects of aging that we cannot outwit, its important to distinguish a superficial fear of growing old, alternatively phrased as literal molecule deterioration, from a philosophical fear of death; the metaphysical cessation of being. Though Im not deaf to the terror of either, the attenuating of the former cant really refute the latter in and of itself. In other words, extending life for its own sake wont do you any good without some kind of moral equipment to boot. However you go about securing this is valid enough so long as it doesnt infringe on the fundamental rights of others. Rabelais lived for ambiguity, Plath was vitalized by the unreal and dangerous, Van Gogh was energized by lifes series of small things, Hitchens lived for irony (and died for it too), and Camus made a point not to think about any of it too intensely.

Chronological age is the most literal translation of our time here, our biological age is the most honest projection of how much of it weve got left, and our reservoir of purpose judges how successfully we spent it. Ultimately, appealing to your temple and the candles that emblazon it, is a good way to neuter the urge to cry over expired milk, whether the curtain falls when youre 25 or 98.

More here:
The biological defects that come with age and how to prevent them - Ladders

While guidelines for psoriatic arthritis recommend a treatment target of remission or low disease activity, consensus is lacking on how to define either. Disease activity is most often measured by DAPSA (Disease Activity index for Psoriatic Arthritis) scorebased mainly on jointsor VLDA/MDA (very low disease activity/minimal disease activity) criteriabased on assessment of joints, skin, and entheses. Previous research indicates that remission/low disease activity rates are higher with the use of DAPSA than with VLDA/MDA, according to Laure Gossec, MD, PhD, but what measurements with either test mean to patients is not well known.

For a study published in Annals of the Rheumatic Diseases, Dr. Gossec and colleagues surveyed patients with psoriatic arthritis of more than 2 years and compared their perceptions of remissions with those of their physicians and VLDA, LDA, and DAPSA scores.

In these patients not selected for good disease control and with usually long disease duration, remission or low disease activity were attained by more than 50% of patients, says Dr. Gossec. Patient-perceived remission/low disease activity was frequent (65.4%). Patient-perceived remission was as frequent as remission based on DAPSA, whereas good status according to VLDA/MDA was reached less frequently. DAPSA-based status appeared to correctly reflect patient-perceived low disease activity, which is an argument to use this score to assess psoriatic arthritis.

As the first to compare treatment targets using composite scores and patient questions on assessment of status, the cross-sectional study used a patient questionnaire developed for this study with patient research partners, but not externally validated. Dr. Gossec also notes that whether the findings would be replicated in patients over time is unknown. She adds, though, that physicians now have more information on patient perceptions of remission, and comparison with composite scores to follow-up patients; DAPSA appeared to agree more with patients assessments, though both scores have strengths and weaknesses.

Comparing patient-perceived and physician-perceived remission and low disease activity in psoriatic arthritis: an analysis of 410 patients from 14 countrieshttps://ard.bmj.com/content/78/2/201

Excerpt from:
Comparing Perceptions of Psoriatic Arthritis Disease Activity - Physician's Weekly

The 2019 annual meeting of the American College of Rheumatology (ACR) had an abundance of sessions dedicated to the management of rheumatoid arthritis (RA).

Novel TreatmentModalities

A large focus of the novel RA treatment sessions were the Janus kinase (JAK) inhibitors. Multiple abstracts regarding upadacitinib, an oral JAK-1 selective inhibitor, were presented. Josef Smolen, MD, of the University of Vienna in Austria, discussed 48-week results of the SELECT-MONOTHERAPY trial (A Study Comparing Upadacitinib [ABT-494] Monotherapy to Methotrexate [MTX] Monotherapy in Adults With Rheumatoid Arthritis [RA] Who Have an Inadequate Response to MTX; ClinicalTrials.gov Identifier: NCT02706951). For patients continuing upadacitinib 15 mg/d, ACR20, ACR50, and ACR70 response was 87%, 70%, and 46%, respectively; ACR20, ACR50, and ACR70 response for upadacitinib 30 mg/d was 87%, 72%, and 54%, respectively. The most frequent treatment-emergent adverse events were infection, particularly herpes zoster, and elevations in creatine phosphokinase and alanine aminotransferase levels.

Efficacy and safety data on filgotinib, another JAK-1 selective inhibitor, were presented by Bernard Combe, MD, of Montpellier University in France. The FINCH1 (Filgotinib in Combination With Methotrexate in Adults With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate; ClinicalTrials.gov Identifier: NCT02889796) study was a phase 3 randomized controlled trial comparing filgotinib 100 mg/d and 200 mg/d with the active comparator, adalimumab 40 mg every 2 weeks, or placebo in addition to a stable dose of methotrexate. The efficacy of filgotinib 200 mg/d was found to be noninferior to adalimumab, achieving a Disease Activity Score in 28 joints/C-reactive protein (DAS28-CRP) score of 3.2 in 60% of participants at week 24.

Updates onPharmacotherapy Safety Data

Several important abstracts regarding pharmacologic safety data in RA were presented at the meeting. Daniel H. Solomon, MD, of Brigham and Womens Hospital in Boston, Massachusetts, presented safety data on methotrexate based on his prespecified secondary analyses of CIRT (Cardiovascular Inflammation Reduction Trial Inflammation Imaging Study; ClinicalTrials.gov Identifier: NCT02576067), which was a randomized controlled trial that included adults with cardiovascular disease and diabetes or metabolic syndrome. Participants were randomly selected to receive low-dose methotrexate (<20 mg/wk) or placebo and were followed for a mean of 27 months. Relative rates of gastrointestinal, infectious, pulmonary, and hematologic adverse events were increased in patients receiving methotrexate compared with participants who were receiving placebo. Notably, there were no differences in the relative rates of malignant, mucocutaneous, neuropsychiatric, musculoskeletal, or renal adverse events.

In addition to upadacitinib as previously mentioned, safetyprofiles of other JAK inhibitors were also presented. Tofacitinib has beenassociated with blood clots in patients who have additional risk factors forthromboembolism. High-dose tofacitinib 10 mg twice daily should not be used inthe treatment of RA. Risk factors for thromboembolism include previouscardiovascular events, cancer, clotting disorders, use of hormonalcontraceptives, and pending major surgery or prolonged immobilization. Datafrom phase 3b/4 trials evaluating tofacitinib 11 mg/d with methotrexate werepresented by Stanley B. Cohen, MD, of the Metroplex Clinical Research Center inDallas, Texas. Importantly, no new safety risks were observed, which wassimilar to that seen with the tofacitinib immediate-release 5 mg twice dailydosage.

A very important and potentially practice-changing updatewas presented by Michael George, MD, of the University of Pennsylvania inPhiladelphia. Dr George analyzed the risk for serious infection associated withlong-term use of glucocorticoids for the treatment of RA. Medicare claims dataon more than 170,000 individuals were used for the analysis. Among older patientswith RA on stable treatment with conventional synthetic and biologic disease-modifyingantirheumatic drugs (DMARDs), prednisone at dosages <5 mg/d weresignificantly associated with increased risk for serious infections. Seriousinfections included urinary infections, pneumonia, bacteremia, and skin or softtissue infections. This study has important management implications forrheumatologists as long-term use of glucocorticoids should be minimized.

Updates onEpidemiology Research in RA

In terms of epidemiology and RA disease trajectory, datafrom the Risk RA Prospective Study were presented by Aase Hensvold of theKarolinska Institute in Stockholm, Sweden. This study followed patients whowere referred to the rheumatology clinic from the primary care setting becauseof positive anti-cyclic citrullinated antibodies but who lacked arthritis uponexamination. A detailed ultrasound evaluation was performed at baseline andfollow-up. Slightly less than half of the enrolled individuals with anti-cycliccitrullinated antibodies developed ultrasound-detectable arthritis at a medianfollow-up time of 11 months. However, participants who had tenosynovitisdetected by ultrasound at baseline were more likely to progress to RA at follow-up.The study highlights the utility of a baseline ultrasound evaluation for thepurpose of prognostication in patients with early or preclinical RA.

Data presented by Elena Myasoedova, MD, PhD, of the MayoClinic College of Medicine and Science in Rochester, Minnesota, explored thechanging epidemiology of RA from a population-based incidence cohort. She foundthat although the incidence of RA has been constant over the past approximately24 years, there has been a decrease in the number of patients with RA withpositive rheumatoid factor and an increase in patients with seronegativedisease. When comparing patients who met the 2010 European League AgainstRheumatism (EULAR)/ACR criteria with those who met the 1987 ACR criteria only,patients in the former group had higher joint counts and were more likely to beever smokers. However, overall the prevalence of smoking declined during the 30-yearstudy period.

Several sessions at the ACR annual meeting featuredcomorbidities in RA. Joshua F. Baker, MD, of the University of Pennsylvania,performed a cross-sectional analysis of diabetes and RA using the VeteransAffairs RA registry. Type 2 diabetes mellitus was present in 26% of patients atenrollment. Multivariable analysis noted that high baseline disease activitywas associated with a greater risk of incident diabetes; prednisone use wascontrolled for in analysis. Interestingly, tumor necrosis factor inhibitor usewas associated with a significantly lower risk for diabetes. This study impliesthat better disease control may lower the risk for subsequent metaboliccomplications such as type 2 diabetes mellitus in patients with RA.

Cardiovascular risk was discussed by Jon T. Giles, MD, ofColumbia University in New York City. Dr Giles presented information about indicatorsof actionable levels of atherosclerosis in patients with RA who traditionallyare labeled as having low or intermediate cardiovascular risk that is based onstandard risk algorithms. Dr Giles found that actionable levels of coronaryartery calcium determined by traditional risk factors such as older age, eversmoking, antihypertensive use, and aspirin use may not necessarily be adequatefor individuals with RA. Particularly, RA disease activity should be anadditional component of the risk algorithm. Using his modified risk algorithm, DrGiles found that a large proportion of patients with RA who were traditionallycategorized as having lower cardiovascular risk may benefit from additionalscreening and prevention strategies. Similarly, Bryant England, MD, of theUniversity of Nebraska, presented data on multimorbidity in RA from acommercial claims database. Compared with baseline enrollment and one-yearfollow-up, the percentage of patients with multimorbidity considerablyincreased for patients with RA compared with those without RA. Therefore, screeningfor and management of chronic conditions in patients with RA is necessary atthe initial visit to prevent the progression of multimorbidity.

The epidemiology of inflammatory arthritis related to immunecheckpoint inhibitors (ICI) that are used in the treatment of cancer waspresented by Tawnie Braaten, MD, of Johns Hopkins School of Medicine in Baltimore,Maryland. Patients with ICI-induced inflammatory arthritis were found to have ratesof seropositivity and persistent disease activity at 3 and 6 months aftercessation of ICIs. Longer duration of ICI use and combination ICIs wereassociated with persistent inflammatory arthritis. Three-quarters of patientsunderwent immunosuppression, which did not appear to affect tumor response.This study is important because the use of ICIs continues to grow in cancertherapy, and patients with resultant inflammatory arthritis will increasinglybe referred to rheumatology practices.

Practice-Changing Updates

Several abstracts related to tapering both conventionalsynthetic and biologic DMARDs were presented at the meeting. In a late-breakingabstract presented by Siri Lillegraven, PhD, of Diakonhjemmet Hospital in Oslo,Norway, patients with RA who were in sustained remission during treatment with conventionalsynthetic DMARDs and who continued therapy tended to have flares less often andwith less radiographic joint progression than patients whose therapy wastapered. The risk of adverse events related to continued therapy on biologicDMARDs and JAK inhibitors was further explored in a meta-analysis presented by DorotheVinson, of Assistance Publique Hospital of Marseille in France. She reportedthat tapering biologic DMARDs and JAK inhibitors did not lead to a decreasedrisk for serious infections, serious adverse events, or malignancy compared withcontinuing treatment.

While the efficacy and safety of pharmacotherapies tend toshape our practice as rheumatologists, Alexis Ogdie-Beatty, MD, of the PerelmanSchool Medicine at the University of Pennsylvania, along with Ben Nowell, PhD,of the Global Healthy Living Foundation in New York City, highlighted thegrowing use of smartphone applications in clinical and research practice. Theirinteresting session titled, Doctor, Should I Get this App? explored therapidly expanding collection of smartphone apps geared toward behavior changes suchas lifestyle improvement with a focus on weight loss, stress, and sleep. Withfurther review by the rheumatology community, these apps may be recommended to patientswith RA to improve certain issues affecting quality of life that may not beamenable to pharmacologic therapies.

Conclusion

There were many interesting and ground-breaking abstractsrelated to RA at this years ACR annual meeting. Data on the safety andefficacy of JAK inhibitors were widely discussed and will continue to be animportant topic of continued research. The decision to taper vs continue conventionalsynthetic and biologic DMARDs in light of important safety data will needfurther investigation. Perhaps with increasing use of mobile technology,monitoring patients between appointments will allow for accelerated research onthe treatment of RA.

See the rest here:
Expert Insights on Rheumatoid Arthritis From the ACR/ARP 2019 Annual Meeting - Rheumatology Advisor

Genetics and weather are coming against Newfoundlanders and Labradorians who have the highest incidence of arthritis in Canada.

One in four Newfoundlanders and Labradorians suffer from one form of arthritis or another.

That from the Arthritis Societys Jennifer Henning. She says arthritis is an inflammation of the joint, but there are some 100 different types of the disease which is split into two major categories, inflammatory and degenerative.

Rheumatoid arthritis is an autoimmune attack on the joints by the bodys own immune system. It can happen at any time, and affect the entire body.

Osteoarthritis is the most common form and comes as the result of wear and tear, injury or the general aging process. It involves a degeneration of the cartilage between the bones of the joint.

Both types of arthritis result in significant pain and loss of mobility.

Henning says unfortunately, weather doesnt help.

She says in laymans terms, the body is tighter because its cold, and when its wet the tissues swell, causing a greater amount of pain and inflammation.

She says genetics also play a strong role especially in the inflammatory type of arthritis.

Rheumatoid arthritis is more common in women and is often triggered by a traumatic event like childbirth, injury or illness.

Originally posted here:
Genetics and Weather in NL Producing Highest Incidence of Arthritis in Canada - VOCM