StemCell Therapy

SALT LAKE CITY, Jan. 06, 2020 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (NASDAQ: MYGN, Myriad or the Company), a global leader in molecular diagnostics and precision medicine, announced that a new analysis of the GUIDED1 clinical trial using the 6-item Hamilton Depression Rating Scale (HAM-D6) was published online in BMC Psychiatry. The key finding is the HAM-D6 scale identified statistically significant improvements in all three clinical endpoints remission, response and symptoms between GeneSight-guided care and treatment-as-usual at Week 8 (Figure 1).

The HAM-D6 scale has been shown to be a better measure of core depressive symptoms than the HAM-D17 scale, said Boadie W. Dunlop, M.D., one of the study investigators and associate professor of Psychiatry and Behavioral Sciences at Emory University School of Medicine. This post hoc analysis provides further evidence that the GeneSight test led to significant and clinically meaningful improvements in clinical outcomes for patients with major depressive disorder relative to treatment-as-usual care.

To view Figure 1: GeneSight Test Significantly Improved Clinical Outcomes by Week 8 (HAM-D6), please visit the following link: https://www.globenewswire.com/NewsRoom/AttachmentNg/980daabb-fd8c-4bbb-b56e-48795fa16bdb

The GUIDED study was the largest prospective study to assess the benefit of pharmacogenomics-guided treatment for depression using the GeneSight Psychotropic test versus an active therapy control arm. All patients in the GUIDED study had the 17-item HAM-D17 questionnaire administered by blinded off-site raters as part of the study protocol. The 6-item HAM-D6 score represents a subset of HAM-D17 questions that have been shown to be more directly linked to depression. For example, questions such as have you had trouble sleeping which could be associated with conditions other than depression are excluded from the HAM-D6 score. Clinical studies have shown that the HAM-D6 score is superior to HAM-D17 at discriminating antidepressants from placebo.

About GeneSight PsychotropicGeneSight Psychotropic is a pharmacogenomic test that analyzes clinically important variations in DNA. The results of the test can inform doctors about genes that may impact how their patients metabolize or respond to depression medications.

About Myriad GeneticsMyriad Genetics Inc., is a leading precision medicine company dedicated to being a trusted advisor transforming patient lives worldwide with pioneering molecular diagnostics. Myriad discovers and commercializes molecular diagnostic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across six major medical specialties where molecular diagnostics can significantly improve patient care and lower healthcare costs. Myriad is focused on five critical success factors: building upon a solid hereditary cancer foundation, growing new product volume, expanding reimbursement coverage for new products, increasing RNA kit revenue internationally and improving profitability with Elevate 2020. For more information on how Myriad is making a difference, please visit the Companys website: http://www.myriad.com.

Myriad, the Myriad logo, BART, BRACAnalysis, Colaris, Colaris AP, myPath, myRisk, Myriad myRisk, myRisk Hereditary Cancer, myChoice, myPlan, BRACAnalysis CDx, Tumor BRACAnalysis CDx, myChoice CDx, EndoPredict, Vectra, GeneSight, riskScore, Prolaris, ForeSight and Prequel are trademarks or registered trademarks of Myriad Genetics, Inc. or its wholly owned subsidiaries in the United States and foreign countries. MYGN-F, MYGN-G.

Safe Harbor StatementThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to a new analysis of the GUIDED clinical trial published online in BMC Psychiatry; and the Companys strategic directives under the caption About Myriad Genetics. These forward-looking statements are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that sales and profit margins of our molecular diagnostic tests and pharmaceutical and clinical services may decline; risks related to our ability to transition from our existing product portfolio to our new tests, including unexpected costs and delays; risks related to decisions or changes in governmental or private insurers reimbursement levels for our tests or our ability to obtain reimbursement for our new tests at comparable levels to our existing tests; risks related to increased competition and the development of new competing tests and services; the risk that we may be unable to develop or achieve commercial success for additional molecular diagnostic tests and pharmaceutical and clinical services in a timely manner, or at all; the risk that we may not successfully develop new markets for our molecular diagnostic tests and pharmaceutical and clinical services, including our ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying our molecular diagnostic tests and pharmaceutical and clinical services and any future tests and services are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with operating our laboratory testing facilities and our healthcare clinic; risks related to public concern over genetic testing in general or our tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of the healthcare system or healthcare payment systems; risks related to our ability to obtain new corporate collaborations or licenses and acquire new technologies or businesses on satisfactory terms, if at all; risks related to our ability to successfully integrate and derive benefits from any technologies or businesses that we license or acquire; risks related to our projections about our business, results of operations and financial condition; risks related to the potential market opportunity for our products and services; the risk that we or our licensors may be unable to protect or that third parties will infringe the proprietary technologies underlying our tests; the risk of patent-infringement claims or challenges to the validity of our patents or other intellectual property; risks related to changes in intellectual property laws covering our molecular diagnostic tests and pharmaceutical and clinical services and patents or enforcement in the United States and foreign countries; risks of new, changing and competitive technologies and regulations in the United States and internationally; the risk that we may be unable to comply with financial operating covenants under our credit or lending agreements; the risk that we will be unable to pay, when due, amounts due under our credit or lending agreements; and other factors discussed under the heading Risk Factors contained in Item 1A of our most recent Annual Report on Form 10-K for the fiscal year ended June 30, 2019, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

Media Contact: Ron Rogers Investor Contact: Scott Gleason (801) 584-3065 (801) 584-1143 rrogers@myriad.com sgleason@myriad.com

1 Greden JF, Parikh SV, Rothschild AJ, et al. Impact of pharmacogenomics on clinical outcomes in major depressive disorder in the GUIDED trial: A large, patient- and rater-blinded, randomized, controlled study. J Psychiatr Res. 2019; 111:59-67.

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New Publication Demonstrates GeneSight Improved All Clinical Outcomes Using HAM-D6 Analysis in Large Prospective GUIDED Study - Associated Press

For all of the hype surrounding gene therapy and gene editing, the precision genetic medicine approach that turned in the best 2019 may have been RNA interference (RNAi). The gene-silencing technique earned its first regulatory approval for a novel targeted delivery method. That may not sound like much to get excited about, but it promises to open up numerous high-value opportunities for RNAi drug developers.

The approval, coupled with promising early-stage clinical results and massive partnership deals, explains why Arrowhead Pharmaceuticals (NASDAQ: ARWR) and Dicerna Pharmaceuticals (NASDAQ: DRNA) erupted higher in 2019. The RNAi drug developers saw their market valuations increase by 450% and 106%, respectively, last year.

While both companies have promise, thepharma stocks are likely to fall in early 2020. What does that mean for investors with a long-term mindset?

Image source: Getty Images.

Shares of Arrowhead Pharmaceuticals had a pretty good first nine months of 2019, but the most impressive gains came in the fourth quarter. The RNAi stock gained heading into the American Association for the Study of Liver Diseases (AASLD) Annual Meeting in November. Investors were eagerly awaiting the results of two drug combinations being developed to treat chronic hepatitis B (CHB) by Johnson & Johnson (NYSE: JNJ) subsidiary Janssen.

The results lived up to the hype. The most impressive data came from a triple combination of an RNAi drug from Arrowhead Pharmaceuticals (now called JNJ-3989), an antiviral drug from Johnson & Johnson (JNJ-6379), and a nucleos(t)ide analog (NA). After 16 weeks of treatment, all 12 individuals in the study achieved at least a 90% reduction in two biomarkers of hepatitis B virus activity.

Investors gobbled up shares of Arrowhead Pharmaceuticals because the triple combination appears to be the industry's best hope for developing the first functional cure for CHB (although it can't be called a functional cure just yet).

Additionally, the RNAi drug candidate in the triple combination is based on a targeted delivery platform called TRiM. The approach is simple: The gene-silencing payload is attached to a special sugar that's absorbed by the liver. Since many RNAi drug candidates need to interact with DNA in liver cells, and the sugars are easily metabolized by the liver (improving safety over prior-generation lipid nanoparticle delivery vehicles), it's a perfect pairing.

It helps that just a few weeks after AASLD, Givlaari from Alnylam Pharmaceuticals (NASDAQ: ALNY)became the first RNAi drug candidate based on a conjugated-sugar delivery method to earn regulatory approval. It also helps that Dicerna Pharmaceuticals landed two massive partnerships in the fourth quarter of 2019 -- both based on its own conjugated-sugar delivery platform. Following those deals, there's now considerable overlap between the pipelines of Arrowhead Pharmaceuticals and Dicerna Pharmaceuticals, which are both all-in on targeted delivery.

RNAi Developer

Partner, Indication

Financial Terms

Arrowhead Pharmaceuticals

Johnson & Johnson, hepatitis B

$175 million up front, $75 million equity investment, up to $1.6 billion in milestone payments, royalties

Arrowhead Pharmaceuticals

Johnson & Johnson, undisclosed

Up to $1.9 billion in total milestone payments for up to three additional drug candidates, royalties

Arrowhead Pharmaceuticals

Amgen, cardiovascular disease

$35 million up front, $21.5 million equity investment, up to $617 million in milestone payments, royalties

Dicerna Pharmaceuticals

Roche, hepatitis B

$200 million up front, up to $1.47 billion in milestone payments, royalties

Dicerna Pharmaceuticals

Novo Nordisk, various liver-related cardio-metabolic diseases

$175 million up front, equity investment of $50 million, an additional $75 million over the first three years, up to $357.5 million per drug candidate, royalties

Data source: Press releases, filings with the Securities and Exchange Commission.

Despite all of the progress from both Arrowhead Pharmaceuticals and Dicerna Pharmaceuticals in 2019, both companies are likely to fall back to Earth a bit following giant run-ups.

Consider that Arrowhead Pharmaceuticals is valued at $6.3 billion at the start of 2020. The company's most advanced drug candidate, ARO-AAT, recently began dosing patients in a phase 2/3 trial in a rare genetic liver disease associated with alpha-1 antitrypsin (AAT or A1AT) deficiency. While that study can be used for a new drug application (NDA), and the drug candidate could achieve over $1 billion in peak annual sales, that alone doesn't support a $6.3 billion valuation.

Meanwhile, the triple combination in CHB could support a market valuation well above $6 billion, especially if it proves to be a functional cure. The drug candidate could eventually earn peak annual sales of over $10 billion in that scenario. But the recent gains were spurred by results in only 12 individuals after 16 weeks of follow-up. A phase 2b trial now underway will enroll 450 patients and follow them for two years. In other words, there's plenty of time for investors to take some gains off the table.

Dicerna Pharmaceuticals is valued a little more reasonably, at just $1.5 billion, but it has only one drug candidate in mid- or late-stage clinical trials. The pipeline programs at the center of recent deals with Roche and Novo Nordisk are still in preclinical development or phase 1 studies; there's little to no clinical data from the programs for investors to survey. While the business will be flush with cash after receiving up-front payments in the coming months, there's a lot of work to be done.

To be clear, both Arrowhead Pharmaceuticals and Dicerna Pharmaceuticals hold a lot of promise. Targeted delivery of RNAi drug payloads into the liver could open up considerable opportunities to treat -- for the first time, in some cases -- rare diseases, viral infections, and cardiovascular ailments. Both companies have even demonstrated early work to target gene-silencing payloads to other cell types, such as muscle tissues, which may open up additional avenues for drug discovery and development.

However, these two RNAi stocks have fallen 10.7% and 12.3%, respectively, since Dec. 3 -- and both are likely to fall a bit further in early 2020. If and when that occurs, investors may want to give each stock, especially Arrowhead Pharmaceuticals, a closer look.

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These 2 Stocks Will Fall After the New Year - Nasdaq

A new, safe and efficient way to coax stem cells into bone cells is reported in a recently published article from STEM CELLS Translational Medicine (SCTM).

DURHAM, N.C., Jan. 6, 2020 /PRNewswire-PRWeb/ -- A new, safe and efficient way to coax stem cells into bone cells is reported in a recently published article from STEM CELLS Translational Medicine (SCTM). The protocol, developed by researchers at the University of Sydney, Australian Research Centre (ARC) for Innovative BioEngineering, could lead to a shift in the treatment of bone regenerative medicine.

Large bone defects and loss due to cancer or trauma can result in scar tissue that impairs the bones' ability to repair and regenerate. The current gold standard therapy, autografting, has inherent drawbacks, including limited availability and donor site morbidity. This leaves researchers seeking an alternative source of bone cells and makes bone tissue engineering a growing field with considerable translational potential.

"The success of induced pluripotent stem cell (iPSC) technology to reprogram fibroblasts into progenitor cells of various lineages offers an exciting route for tissue repair and regeneration," said Zufu Lu, Ph.D., a member of the University of Sydney's Biomaterials and Tissue Engineering Research Unit and a research associate at the ARC for Innovative BioEngineering. He is a co-lead investigator of the SCTM study, along with Professor Hala Zreiqat, Ph.D., head of the research unit and director of the ARC Training Centre for Innovative BioEngineering.

"However, while iPSC technology represents a potentially unlimited source of progenitor cells and allows patients to use their own cells for tissue repair and regeneration thus posing little or no risk of immune rejection the technology has several constraints. Among them are the requirement for complex reprogramming using the Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc). To add to the complexity, specific stimuli are required to direct iPSCs to re-differentiate to progenitor cells of the lineage of interest.

"In addition," Dr. Lu said, "any remaining iPSCs pose the risk of tumors following implantation."

One potential way around this, as demonstrated by recent studies, is through the direct reprogramming of fibroblasts into bone cells. "Fibroblasts are morphologically similar to osteoblasts. Their similar transcriptomic profiles led us to hypothesize that distinct factors produced by osteoblasts may be capable of coaxing fibroblasts to become osteoblast-like cells," Prof. Zreiqat said.

Previous studies aimed at using fibroblasts to produce various cell types relied on the genetic manipulation of one or more transcription regulators. But just as with iPSCs, reprogramming fibroblasts in this manner has its own inherent technical and safety issues. The Lu-Zreiqat team, however, surmised that an approach employing natural factors might just allow better control over reprogramming and improve the safety.

"Unlike genetic reprogramming, chemical induction of cell reprogramming is generally rapid and reversible, and is also more amenable to control through factor dosage and/or combinations with other molecules," Dr. Lu explained.

The team initially determined that media conditioned by human osteoblasts can induce reprogramming of human fibroblasts to functional osteoblasts. "Next," said Prof. Zreiqat, "our proteomic analysis identified a single naturally bioactive protein, insulin growth factor binding protein-7 (IGFBP7), as being significantly elevated in media conditioned with osteoblasts, compared to those with fibroblasts."

This led them to test IGFBP7's ability as a transcription factor. They found it, indeed, successfully induced a switch from fibroblasts to osteoblasts in vitro. They next tested it in a mouse model and once again experienced success when the fibroblasts produced mineralized tissue. The switch was associated with senescence and dependent on autocrine IL-6 signaling.

"The approach we describe in our study has significant advantages over other commonly used cell sources including iPSCs and adult mesenchymal stem cells," Dr. Lu and Prof Zreiqat concluded.

"Bone tissue engineering is a growing field where cell therapies have considerable translational potential, but current cell-based approaches face limitations," said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. "The novel observation described in this study could potentially lead to a shift in the current paradigm of bone regenerative medicine."

Story continues

This study was conducted in collaboration with the Charles Perkins Centre and the Children's Hospital at Westmead, University of Sydney.

The full article, "Reprogramming of human fibroblasts into osteoblasts by insulin-like growth factor binding protein 7," can be accessed at https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/sctm.19-0281.

About STEM CELLS Translational Medicine: STEM CELLS Translational Medicine (SCTM), co-published by AlphaMed Press and Wiley, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices. SCTM is the official journal partner of Regenerative Medicine Foundation.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes two other internationally renowned peer-reviewed journals: STEM CELLS (http://www.StemCells.com), celebrating its 38th year, is the world's first journal devoted to this fast paced field of research. The Oncologist (http://www.TheOncologist.com), also a monthly peer-reviewed publication, entering its 25th year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. All three journals are premier periodicals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines.

About Wiley: Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical and scholarly journals, combined with our digital learning, assessment and certification solutions, help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company's website can be accessed at http://www.wiley.com.

About Regenerative Medicine Foundation (RMF): The non-profit Regenerative Medicine Foundation fosters strategic collaborations to accelerate the development of regenerative medicine to improve health and deliver cures. RMF pursues its mission by producing its flagship World Stem Cell Summit, honouring leaders through the Stem Cell and Regenerative Medicine Action Awards, and promoting educational initiatives.

SOURCE STEM CELLS Translational Medicine

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New protocol could signal shift in bone regenerative medicine - Yahoo Finance

6 January 2020

Leading figures in science and healthcare have been recognised in the UK's New Year's Honours list 2020.

Professor Dame SallyDavies received Dame Grand Cross of the Order of the Bath (GCB) for services to public health and research, having previously been made a Dame in 2009. Dame Sally was Chief Medical Officer for England from 2010-2019. Her initiatives included the 'Generation Genome' report (see BioNews908) which recommended widespread adoption of genomic medicine within the NHS, as well as ongoing efforts to combat antimicrobial resistance.

'I am honoured to receive this GCB recognising the efforts of many people across Government, the NHS and beyond, working together on issues ranging through health research and public health to fighting the rise of antimicrobial resistance both in the UK and across the world. We willcontinue to build coalitions for action as this war to save lives is not over' she said.

Professor Lesley Regan who stepped down as President, Royal College of Obstetricians and Gynaecologists (RCOG) in December, was made a Dame 'for services to women's healthcare'.

'I am delighted and honoured to be recognised in the New Year Honours. The progress we have made in women's health at the RCOG is only possible because of the hard work and commitment of the wonderful staff and our wider membership. We have much work to do to achieve the aims set out in the Better for Women report and I look forward to supporting the RCOG and its many key partners to transform healthcare services for women and girls.'

Other honours included a knighthood for Genomics England's former chair, Jonathan Symonds for services to UK life sciences and finance.

Professor Alan Lehmann, Research Professor of Molecular Genetics, University of Sussex received a CBE for services to medical science, patients and families affected by the genetic conditions xeroderma pigmentosum and Cockayne syndrome.

OBEs were awarded to Professor Sheila McLean, the University of Glasgow's Professor Emerita of Law and Ethics in Medicine for services to health and education and to former director of the Academy of Medical Sciences Dr Helen Munn for services to the advancement of medical science.

Nicola Perrin, former head of the Wellcome Trust's Understanding Patient Data programme received an MBE for services to science.

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Professors Sally Davies and Lesley Regan recognised in New Year's Honours - BioNews

NuProbe Global and CarrierGene Biotech Co. Ltd. (Suzhou, China) announced the successful completion of their recent merger and integration. The new company will operate under the English brand NuProbe Global and the Chinese brand (Yue Er).

We are very excited about the merger between NuProbe and CarrierGene, said Yingshuang Chai, who is the co-founder and former CEO of CarrierGene and now serves as CEO and Chairman of the Board of Directors of the merged NuProbe.

Mr. Chai is a renowned expert in the genomics industry with nearly 20 years of success and rich experience in market operation. He is the former national clinical business director of Life Technologies China and the former national director of clinical strategy & development of Thermo Fisher China.

I am greatly impressed by NuProbes technology, which is highly differentiated with unique features that are hard to mimic using alternative methods. The platform innovation can break through the current bottlenecks of the clinical genetic testing and enable new business models, Chai continued. After the merger, NuProbe will have exceptional research and commercial teams in both the United States and China. In addition to new products to be deployed in the US, China, and the Asia-Pacific region, our technology can help other genomics companies achieve better technical performance, go beyond homogenous competition, and accelerate the expansion of the entire genomics diagnostic market. In the past six months, we have completed the integration of the two companies products, finances, teams, and business, and made breakthrough progress with the development of new products.

NuProbe has several groundbreaking cross-platform molecular technologies that greatly improve the technical performance of different molecular diagnostic platforms. CarrierGene has been a pioneer and leader in the blue ocean market of infertility gene testing in the field of reproductive health. The merged NuProbe will accelerate the commercialization of various cutting-edge technologies, empower existing technology platforms and business partners, create more products adapted to clinical applications, and enable new advances in the genomics market. The merged NuProbe will have research and development (R&D) laboratories in Houston, TX and Shanghai, China, as well as a Good Manufacturing Practice (GMP) production facility in Suzhou, China.

Mr. Chai is an amazing entrepreneur with a precise and profound understanding of the Chinese genomics industry after years of immersion, and extraordinary insights and vision. I look forward to seeing NuProbe grow into a great enterprise under his leadership and contributing to the molecular diagnostics industry in China and around the world, said Peng Yin, Ph.D., co-founder of NuProbe, who is also a professor of systems biology at Harvard Medical School and a core faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard University.

Both our R&D teams and commercial teams have enjoyed working together as business partners in the past year, and the formal merger will allow closer and more efficient collaboration, said David Zhang, Ph.D., co-founder of and head of innovation at NuProbe, and associate professor of bioengineering at Rice University.

Yundi Chen, Ph.D., co-founder of and CTO at CarrierGene, added: NuProbes technologies not only have strong applications in cancer, but are also well suited for many clinical challenges in genetic diseases and reproductive health. This merger will allow our two companies to more effectively penetrate our respective core markets while opening up new opportunities.

The synergy between NuProbes technology and CarrierGenes commercial team is formidable. I am very happy to support the founding of NuProbe and facilitate the merger of NuProbe and CarrierGene. With the completion of the merger, we are optimistic that NuProbe will become an innovative diagnostic company rooted in China and leading the world, said Kevin Chen, founding partner of BioTrack Capital and a member of the Board of Directors of the merged NuProbe. BioTrack is enthusiastic to support the merged NuProbe with an initial investment.

The investment by BioTrack Capital will support R&D in new product development, filing of NMPA (Chinas equivalent of FDA) registrations for in vitro diagnostic products, and commercial team buildout.

We believe that the merged NuProbe will rapidly realize the commercialization of its world-leading core technology. We are optimistic about the companys prospects, and fully support Mr. Chai and his team, said Trency Gu, managing director at Sequoia Capital China and a member of the Board of Directors of NuProbe.

Ms. Gu will continue to serve as a member of the Board of Directors of the merged NuProbe.

The revolutionary technologies developed by NuProbe will be strong assets for the merged company, said Dongmei Ji, founding partner at GP Healthcare Capital. GP Healthcare Capital is one of the Pre-A investors of CarrierGene and has appointed Ms. Xiaoyan Wang as a member of the Board of Directors of the merged NuProbe.

NuProbes technology is widely recognized for its innovation and unique capabilities. The merger with CarrierGene will result in more products that benefit patients in a wider range of disease indications, said David R. Walt, Ph.D., member of the National Academy of Engineering and the National Academy of Medicine, co-founder of Illumina, professor of pathology at Harvard Medical School, and a core faculty member of the Wyss Institute at Harvard University.

We look forward to continuing to support the merged NuProbe in driving more technology innovations to improve human health, Dr. George Church,

member of the National Academy of Sciences and the National Academy of Engineering, professor of genetics at Harvard Medical School, and a core faculty member of the Wyss Institute, added.

Both Dr. Walt and Dr. Church will continue to serve on the Scientific Advisory Board of the merged NuProbe.

In addition, the merged NuProbe has executed a contract for a strategic partnership with Illumina in late 2019. NuProbe and Illumina will work together in the field of clinical NGS testing for infertility and other genetic diseases. As part of the collaboration, NuProbe will develop clinical molecular diagnostic kits, including for nucleic acid extraction, library construction, and bioinformatic software. The kits will be used on Illuminas NGS instruments, and the two companies will seek regulatory approval from NMPA. Further potential collaborations between NuProbe and Illumina are in discussions.

To learn more about NuProbe, please visit http://www.nuprobe.com.

About NuProbe Global

NuProbe Global is a biotech company founded by world-class scientists in 2016, building initially on several technologies exclusively licensed from Harvard University and Rice University, and financed by prestigious institutional investors such as Sequoia Capital China. NuProbe possesses a number of revolutionary molecular diagnostics technologies, and collaborates with many renowned academic institutions, medical institutions, and companies worldwide. It has subsidiaries in Houston, USA and Suzhou, China. http://www.nuprobe.com

About CarrierGene Biotech Co. Ltd.

Founded in 2016, CarrierGene was co-founded by former senior employees from first-line companies in the genomics industry such as Thermo Fisher, Illumina and WuXi AppTec. Building on the blue ocean market of infertility in reproductive health, CarrierGene is committed to using advanced genetic testing technology and data analysis algorithms to identify the causes of infertility for patients, facilitate follow-up treatment, and increase the birth rate of the population. CarrierGene is the driver and leader in the infertility field of China. CarrierGene has a GMP facility in Suzhou and an R&D and marketing center in Shanghai. Several products have already entered the clinical registration stage.

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NuProbe Global and CarrierGene Biotech Co. Ltd. Announced Completion of Merger, Appointed Yingshuang Chai as CEO, and Established Collaboration with...

Dr Jeremiah Stamler has a little problem at work.

You know the kind: that checklist item that you cant quite seem to check, the one part of the big project that you havent yet nailed down.

You cant slam the door shut on the work until you get answers.

He knows the problem is out there, just waiting for him. And frankly, thats just the kind of thing he thrives on.

Dr Stamler is a professor emeritus and active researcher at the Northwestern University Feinberg School of Medicine in the United States, who recently turned 100 years old.

His problem is cheese.

Dr Stamlers speciality is preventive medicine in fact, he helped invent the field.

He did pioneering research into the causes of heart disease and coined the term risk factors to describe circumstantial and genetic contributors that increase the risk of cardiovascular disease.

While working for Chicagos Public Health Department in the 1960s, he developed the Heart Disease Control Program, aimed at educating the public and bringing focus to issues the city still grapples with, such as the availability of healthy food in poor neighbourhoods.

Hes an early adopter of whats known today as the Mediterranean diet and his own best advertisement, a long-living testament to the lifestyle changes he advocates.

Currently, hes one of only a tiny handful of scientists over age 90 to have an active US National Institutes of Health grant for research.

We have immense amounts of things we should be grateful to Dr Stamler for, says Dr Donald Lloyd-Jones, chair of Northwesterns Department of Preventive Medicine, because hes improved our health as a nation and a world, but hes also affected our society.

He points out that Dr Stamler, who founded the Department of Preventive Medicine, has retained 110% of his mental acuity. Hes forgotten more than I will ever know, and I dont think hes forgotten very much.

But aside from being an obvious outlier in the healthy-habits-plus-great-genes department, the record of Dr Stamlers life reveals another core characteristic that clearly fuels him.

Hes charming and smart, but he wont back down.

Not for anything. Not for big food companies or basic human intransigence, or even the US Congress. Not for the toll age takes, not even for time.

He has made standing up for things his stock-in-trade.

I think its a measure of his character, says Dr Lloyd-Jones. Its remarkable. Hes my hero.

A life in research

Dr Stamler was born in Brooklyn, New York, in 1919, and grew up in West Orange, New Jersey, the child of Russian immigrants.

From an early age, he was suspicious of mass-market food.

The loaf of white bread is anathema, he says. My father got to this country, saw the white bread and was ready to get back on the boat and go home!

Instead, he grew up with hearty rye breads and got an early start eating whole grains.

Other healthy habits came easy, he says: I never liked butter. I dont know why. It mustve been something in the blood intuitive.

After medical school, he did what most of his contemporaries were doing and entered the US Army.

Near the end of World War II, he was sent overseas. To Bermuda, he says. So I spent a lovely year in Bermuda, my wife came with me, and it was very nice.

Shortly thereafter, the war ended, and like thousands of other GIs, he headed home to launch the next phase of his life.

He knew he wanted that life to be in research, and in 1947, found a place to pursue that work, taking a position at Michael Reese Hospital in Bronzeville, Chicago, under pioneering cardiology researcher Dr Louis Katz.

Dr Katz told me, Why the hell do you want to go into research? says Dr Stamler.

You never win. When you first discover something, people will say I dont believe it.

Then you do more research and verify it, and theyll say, Yes, but...

Then you do more research, verify it further and theyll say, I knew it all the time.

And he was right.

Undeterred, Dr Stamler and his first wife Rose, who trained as a sociologist, but went on to become a major researcher in the fields of cardiovascular disease and hypertension in her own right, moved to Chicago in 1947.

They offered me a US$200-a-month fellowship, he says. In those days, that was a fortune.

His research involved examining the effects of cholesterol and other factors suspected as drivers of cardiovascular disease.

I was always interested in the heart artery problem. Why did human beings with diabetes get more heart artery disease?

Whats the relation of habitual lifestyle, fat intake, saturated fat intake, cholesterol intake, salt intake, with cardiovascular disease? The interplay between multiple factors.

And of course, we were all interested in tobacco even way back then.

He studied his theories on animals.

I was feeding cholesterol to chickens, he says. We could test everything that we suspected might have an impact, except smoking.

And over time, he helped discover and confirm many of the things we now take for granted: High cholesterol and high blood pressure are linked to cardiovascular disease.

Into public health

Dr Stamlers interest in these issues didnt stop at the merely scientific, however.

He had long been interested in social causes he and Rose had met at student meetings during World War II, while he was still in college, and her work leaned strongly into social justice.

He realised that his work had vast implications in the world outside the laboratory.

From 1948 on, as our work accelerated, he says, we were more inclined to translate our findings into recommendations for the public.

That approach began to earn him a few enemies.

Here in Chicago, we had the North American Meat Institute, they were barking at me all the time.

They had a very simple view: Why dont you do research, write papers, publish them and shut up?

We didnt feel that was an appropriate posture for people doing research on a scientific problem of great public health importance to do the research and then bury it. What the hell is the point?

Big tobacco, big food companies and other interest groups werent too happy about Dr Stamlers findings either.

He didnt care. I began to find the best ways to express all this to the public, and we decided that the best way is the risk factor concept, he says.

A set of well-defined traits, easily measured, frequently occurring, which when pre-sent, particularly in combination, are greatly associated with increased risk.

Risk factors, which represented something the public could understand and act to change, changed the face of how Americans thought about cardiovascular health.

The question was, what happens when you modify them, control them, lower them? Dr Stamler says.

Does the cigarette smoker at age 60, after more than 40 years of smoking, benefit from quitting smoking and lowering cholesterol?

The answer is, it isnt too late.

Dr Stamler was driven by a desire to see that knowledge put into practice by the public.

Its a very important message, he says. From a practical point of view, its the only message.

In 1958, he brought that activist approach to public health to city government, taking a position in Chicagos Department of Public Health.

I rolled up my sleeves and went formally to work, he says. A different kind of work. Quite different from feeding cholesterol to chickens.

Reluctantly, he gave up animal research and turned his attention to the pressing concerns of the citys health.

We started with rheumatic fever prevention in kids, he says.

We developed a hypertension control programme, coronary prevention evaluation programme, all right there in (then Chicago Mayor Richard J) Daleys Health Department.

He actually used a picture of me with one of the participants in the programmes in one of his political campaigns, to show how up-to-date and modern his administration was.

Dr Stamler also looked to tackle Chicagos diet: First and foremost, we worked to improve the mix of foods that were readily available in the supermarket.

We encouraged broiling rather than frying, roasting on a rotisserie rather than frying, modest portion sizes.

Chicagos legendary steakhouses? They didnt exactly fit Dr Stamlers programme.

It may be OK to victimise a tourist by selling him a 16-ounce (455g) steak, he says, but for the natives, lets make it a 4- or 5-ounce (113g or 142g) steak.

Lets encourage fish and seafood, vegetables and fruits, whole grains.

Not that were indifferent to the outside, but we feel a first responsibility to locals.

The question of the role cheese, as seen in this filepic, plays in heart disease is what currently occupies centenarian researcher Dr Stamlers thoughts.

An un-American accusation

But it wasnt steakhouses or even food lobbyists who posed Stamlers next challenge.

In 1965, he was called before the US House Un-American Activities Committee (HUAC), a congressional committee aimed at ferreting out suspected communist sympathisers in America.

The committee was known for subpoenaing a range of people, from the entertainment industry, academia and other spheres of public life.

They had informants who told them who to call, says Tom Sullivan, an attorney who worked on Dr Stamlers HUAC case, and the people took the Fifth Amendment (to the US Constitution, invoking a right against self-incrimination) and that was the end of it.

It ruined many lives and employment and wreaked havoc.

The consequences for refusing to answer the committees questions was blacklisting, and in Dr Stamlers case, Sullivan says, Mayor Daley would have fired him immediately.

Dr Stamler chose not to exercise a right against self-incrimination, instead choosing not to answer the committees questions to him by challenging its constitutional right to do so.

Sullivan and his team filed suit against the committee on behalf of Dr Stamler and his colleague Yolanda Hall, who worked as a nutritionist in his department and was also an outspoken activist on issues such as fair housing and civil rights.

The committee found the pair in contempt of the US Congress.

The clients were facing years in jail for contempt of Congress, says Sullivan, and Jerry Stamler decided he was willing to take that chance, to make this a test case.

Litigation followed for eight-and-half years, during which Dr Stamler continued to champion public health, but rarely spoke publicly about the court battle.

In late 1973, the case settled, with the committee, which had begun to lose steam, backing down and Dr Stamlers side agreeing to withdraw its complaint.

In 1975, HUAC was disbanded. The case, says Sullivan, was the decisive factor in ending it.

Those who know Dr Stamler best say the story isnt out of character.

He has a mantra, says Dr Lloyd-Jones, just apply firm, steady pressure.

When his scientific discoveries or medical recommendations meet resistance, Dr Lloyd-Jones says, his response is always the same: Keep smiling. But dont back down.

He knows that if you apply firm, steady pressure over time, the data will win the day.

If we make sure our assertions are grounded in the very best science, the truth will out.

Confronting cheese

In 1972, Dr Stamler was appointed as the founding director of the Department of Community Health and Preventive Medicine at Northwestern, where his research continued and he took on the role of mentor to a stream of new cardiologists and researchers.

The work has never let up, though Dr Stamler has decided where to draw the line in one arena.

He sort of stopped advancing in his tech use at fax machines, says Dr Lloyd-Jones, so when we send him papers to read, we email them to his assistant, they print them out, he takes the hard copy, he marks them up extensively in pen, and he faxes them back.

Currently, Dr Stamlers working with a team on metabolomics, the study of products created by the bodys metabolic processes.

Those faxed notes, Dr Lloyd-Jones says, are sharp as ever.

Hes really at his core a scientist. Hes always about taking the data and what it is giving you, and not over-interpreting it.

Dr Stamler sticks to his guns at home as well.

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Father of preventive medicine, Dr Jeremiah Stamler, turns 100 - The Star Online

A 3-year-old western lowland gorilla named Leslie at the San Diego Zoo Safari Park developed a traumatic cataract. After a UC San Diego Health surgeon successfully removed the cataract, Leslie returned to her playful antics alongside the rest of the Safari Park troop. Photo by San Diego Zoo Global

Animal care specialists at the San Diego Zoo Safari Park were concerned when they noticed cloudiness in the left eye of Leslie, a 3-year-old female western lowland gorilla. Closer inspection confirmed the lens had changed and the left eye was shifting haphazardly, prompting Leslie to favor use of her right eye.

Given Leslies young age and developmental stage, Safari Park veterinarians organized a team of internal and external experts, including ophthalmologists and anesthesiologists at UC San Diego Health, to perform the Parks first-ever cataract surgery on a gorilla.

As veterinarians, we are experts in our species but we are not necessarily specialists in all of the different fields of medicine, said Meredith Clancy, DVM, San Diego Zoo Safari Park associate veterinarian. We rely heavily on the amazing community we have here in San Diego to help us out.

On December 10, 2019, surrounded by animal care experts and veterinarians in khaki uniforms and UC San Diego Health medical team members in scrubs, Leslie rested comfortably in the operating room at the San Diego Zoo Globals Paul Harter Veterinary Medical Center. A pharmaceutical muscle blocker prevented even the slightest of movement, allowing Chris W. Heichel, MD, cataract surgery specialist at Shiley Eye Institute at UC San Diego Health, to perform the delicate procedure.

Heichel and his team employed a specialized microscope and instruments designed for cataract surgery to successfully remove the cataract in Leslies left eye using gentle suction. Once the cloudy lens was removed, a new artificial lens was inserted, which is designed to provide Leslie with clear vision for the rest of her life.

Chris W. Heichel, MD, cataract surgery specialist at Shiley Eye Institute at UC San Diego Health, and his team employed a specialized microscope and instruments designed for cataract surgery to successfully extract a cataract in the left of 3-year-old gorilla at the San Diego Zoo Safari Park. Photo by Ken Bohn, San Diego Zoo Global

While Heichel has performed thousands of eye surgeries on human patients, ranging in age from one day to 105 years, this was his first surgery on a gorilla.

Fortunately, the similarities between the anatomy of human and gorilla eyes are great enough to allow us to safely navigate the procedure without complication, said Heichel. The remainder of the eye appeared to be in excellent health, indicating exceptional vision potential for the rest of Leslies life.

A cataract is a clouding of the clear lens behind the colored part of the eye, known as the iris. Cataracts typically develop over time, as part of the normal aging process, but they can also be caused by trauma to the eye. Once a cataract develops, the lens becomes progressively cloudier and vision deteriorates.

Heichel, Clancy and animal caregivers suspect that Leslies cataract was a result of an injury, either from a fall while the youngster was practicing her climbing skills or from an overly rambunctious play session with other young gorillas in her troop.

As she recovers, Leslie will require both topical and oral antibiotics and steroids to prevent infection and to control postoperative inflammation, said Clancy. Leslie will be monitored closely, but she is already back with her troop in the Gorilla Forest habitat at the Safari Park.

Following successful healing, the remaining concern is the possibility of cloudiness recurring.

The eye has an envelope that holds the lens in place. It should remain clear, but sometimes after cataract surgery, the envelope will get a little cloudy, said Heichel, professor of ophthalmology in the Viterbi Family Department of Ophthalmology at UC San Diego School of Medicine. In a human patient, we can laser the envelope to remove the cloudiness. That might not be quite so easy for Leslie, therefore I made a little opening in the back of the envelope to maintain her clear vision in the future. I am grateful for the chance I had to work with the exceptional San Diego Zoo Global team to help have a positive impact on Leslies life.

Because of Leslies age, the Safari Parks animal care team was concerned her 31-year-old mother, Kokamo, might be upset about Leslies absence from the gorilla habitat during the procedure. They elected to anesthetize Leslie and Kokamo at the same time, and use the opportunity to perform a routine health check on Kokamo, which included dental, cardiac and overall physical assessments. The results of Kokamos exam showed that she continues to be in good health.

About San Diego Zoo GlobalAs an international non-profit organization, San Diego Zoo Global works to fight extinction through conservation efforts for plants and animals worldwide. With a history of leadership in species recovery and animal care, San Diego Zoo Global works with partners in science-based field programs on six continents, and maintains sanctuaries and public education facilities in many places. Inspiring passion for nature is critical to saving species, and San Diego Zoo Globals outreach efforts share the wonder of wildlife with millions of people every year. Current major conservation initiatives include: fighting wildlife trafficking and the impacts of climate change on wildlife species; broad-spectrum species and habitat protection efforts in Kenya, in Peru and on islands worldwide; preventing extinction in our own backyard; and expanding efforts to bank critical genetic resources and apply them to the conservation of critically endangered species. To learn more, visit sandiegozooglobal.org or connect with us on Facebook.

About UC San Diego HealthUC San Diego Health, the regions only academic health system, is dedicated to delivering outstanding patient care through commitment to community, groundbreaking research and inspired teaching. For 2019-20, U.S. News & World Report ranked UC San Diego Health among the nations best in four adult medical and surgical specialties, including pulmonology, geriatrics, neurology and cardiology. The 808-bed academic health system includes UC San Diego Medical Center in Hillcrest and Jacobs Medical Center, Sulpizio Cardiovascular Center, Moores Cancer Center, Shiley Eye Institute, Koman Family Outpatient Pavilion and Altman Clinical and Translational Research Institute, all in La Jolla, as well as primary care and same-day services at clinics throughout Southern California. For more information, visit health.ucsd.edu.

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Experts Come Together to Save 3-year-old Gorilla's Eyesight at San Diego Zoo Safari Park - UC San Diego Health

For all of the wondrous potential of immunotherapies, there have been some notable obstacles in the early goings. Engineering immune cells to attack cancerous tumors can lead to solid results shortly after administering a dose, but for many patients the effects wear off once rapidly mutating tumor cells acquire new defense mechanisms.

Cellectis (NASDAQ:CLLS) thinks it may have a partial solution. In mid-November, the gene editing company published the results from a proof of concept study for its "smart" immunotherapy approach. Is the technique the future of cellular medicine?

Image source: Getty Images.

Today, cellular oncology therapies genetically engineer immune cells to bolster their safety and efficacy as a cancer treatment. There are T cells, natural killer (NK) cells, tumor infiltrating lymphocytes (TILs), and others. They're often engineered with chimeric antigen receptors (CARs) or T cell receptors (TCRs), which allow them to home in on and suppress specific genes in cancer cells.

While current-generation CAR T cells or CAR NK cells are capable of mounting formidable attacks on tumors at first, treatment responses aren't durable for all patients. That's because cancer cells mutate to rely on different proliferation genes, or secrete new molecules into the tumor microenvironment that neutralize immune cells. Meanwhile, overstimulating the immune system can reduce the potency of immune cells and lead to devastating side effects, such as cytokine release syndrome.

That prompted Cellectis to design "smart" CAR T cells capable of adapting to changes in the tumor microenvironment. In a proof of concept study, the company utilized synthetic biology concepts to rewire genetic circuits in three different genes of the initial T cells.

One edit made the immunotherapy more potent, but in a controlled manner to reduce off-target toxicity. The other two edits imbued CAR T cells with the ability to secrete inflammatory proteins inside the tumor microenvironment in proportion to the concentration of cancer cells.

In other words, the smart CAR T cells only asked for help from the rest of the immune system when it was needed most, which increased the anti-tumor activity of treatment and made native immune cells less likely to become neutralized. That should reduce the likelihood of triggering cytokine release syndrome, the most common (and potentially fatal) side effect of cellular medicines, which is caused by high concentrations of immune cells.

The study was conducted in mice, which means the safety and efficacy observations can't be extrapolated into humans. But that wasn't the point. The proof of concept demonstrates that the basic idea of engineering tightly controlled genetic circuits into immunotherapies is feasible. It could even allow multiple genetic circuits of the same drug candidate to be tested against one another in parallel, hastening drug development and lowering costs. Is it the inevitable future of cellular medicine?

Image source: Getty Images.

Gene editing tools are required to engineer immune cells. In fact, immunotherapies are the lowest hanging fruit for gene editing technology platforms today. It's simply easier to engineer immune cells in the lab (ex vivo) than it is to engineer specific cell types in the complex environment of the human body (in vivo).

That explains why nearly every leading gene editing company has immunotherapy programs in its pipeline. Coincidentally, all of the leading drug candidates in the industry pipeline are off-the-shelf CAR T cells engineered to treat CD19 malignancies such as non-Hodgkin's lymphoma (NHL) and B-acute lymphoblastic leukemia (B-ALL), regardless of the gene editing approach used. The smart CAR T cells designed by Cellectis targeted CD22 malignancies, but the approach could be adapted to CD19 antigen.

Developer(s)

Drug Candidate

Gene Editing Approach

Development Status

Cellectis and Servier

UCART19

TALEN

Phase 2

Precision BioSciences (NASDAQ:DTIL)

PCAR0191

ARCUS gene editing

Phase 1/2

CRISPR Therapeutics (NASDAQ:CRSP)

CTX110

CRISPR-Cas9

Phase 1/2

Sangamo Therapeutics (NASDAQ:SGMO) and Gilead Sciences (NASDAQ:GILD)

KITE-037

Zinc finger nuclease

Preclinical

Data source: Company websites.

Will these companies eventually turn to "smart" immunotherapies with regulated genetic circuits? It does seem inevitable, especially if the approach can reduce or eliminate cytokine release syndrome and enable more durable responses.

For example, Cellectis reported that all seven patients taking part in the phase 1 trial of UCART19 suffered from at least grade 1 cytokine release syndrome, which caused complications that led to the death of one patient. Five of the seven patients achieved molecular remission, but one relapsed (and remained alive) and one died. To be fair, all patients taking part in the trial had advanced, heavily pretreated B-ALL.

Precision BioSciences has encountered similar obstacles in an ongoing phase 1/2 trial of PBCAR0191. The company's lead drug candidate was administered to nine patients with NHL or B-ALL. Three cases of cytokine release syndrome were reported, but all were manageable. Seven responded to treatment, including two that achieved a complete response, but three eventually relapsed.

CRISPR Therapeutics recently began dosing patients with CTX110 in a phase 1/2 trial that will eventually enroll up to 95 individuals, but initial results won't be available until 2020. Sangamo Therapeutics and Kite Pharma, a subsidiary of Gilead Sciences, are plowing ahead with zinc fingers,but are still in preclinical development.

Investors seem pleased with most of these gene editing stocksright now. After all, despite the obstacles, current-generation cellular medicines are delivering impressive results in patient populations with relatively few options. But upcoming data readouts could easily differentiate the pack. That could increase the need to invest in augmented capabilities, such as smart immunotherapies.

There's plenty of untapped potential in cellular medicine. Today, companies are developing drug candidates with engineered CARs and TCRs designed to test hypotheses about the function of immunotherapies. As approaches find success, measured in safer and more durable responses, the next layer of complexity will be added in an effort to find even more successful therapies. And the cycle will continue.

Therefore, it seems inevitable that the field of cellular medicine will turn to smart immunotherapies with more complex genetic edits, much like the field quickly embraced the need for engineered immune cells and off-the-shelf manufacturing processes. That said, the immediate focus for Cellectis and its peers is building a stable foundation -- and those efforts have only just begun.

More here:
Did Cellectis Just Provide a Glimpse of the Future of Cellular Medicine? - The Motley Fool

Media Advisory

Friday, December 27, 2019

Findings from NIH-funded study could inform treatment strategies.

Identical twins with autism spectrum disorder (ASD) often experience large differences in symptom severity even though they share the same DNA, according to an analysis funded by the National Institutes of Health. The findings suggest that identifying the causes of this variability may inform the treatment of ASD-related symptoms. The study was conducted by John Constantino, M.D., of Washington University School of Medicine in St. Louis, and colleagues. Funding was provided by NIHs Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The study appears in Behavior Genetics.

ASD is a developmental disorder that affects how a person behaves, interacts with others and learns. Previous studies have found that when one identical twin has ASD, chances are extremely likely that the other twin has it, too.

The authors analyzed data from three previous studies comprising a total of 366 identical twin pairs with and without ASD. The severity of autism traits and symptoms in the twins was measured by a clinicians assessment or by parents ratings on a standardized questionnaire. Some cases were diagnosed by both methods. The researchers determined a 96% chance that if one twin has ASD, the other has it, too. However, symptom scores varied greatly between twins diagnosed with ASD. The researchers estimated that genetic factors contributed to only 9% of the cause of trait variation among these twins. In contrast, among pairs of identical twins without ASD, the scores for traits were very similar.

The study authors do not know the reasons for differences in symptom severity, but they rule out genetic and most environmental causes because the twins share the same DNA and were raised in the same environment. Additional studies are needed to determine the cause.

Alice Kau, Ph.D., NICHD Intellectual and Developmental Disabilities Branch, is available for comment.

Castelbaum, L. On the nature of monozygotic twin concordance for autistic trait severity: A quantitative analysis. Behavior Genetics.2019.

About theEunice Kennedy ShriverNational Institute of Child Health and Human Development (NICHD): NICHD conducts and supports research in the United States andthroughout the world on fetal, infant and child development; maternal, child and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visitNICHDs website.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

###

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Severity of autism symptoms varies greatly among identical twins - National Institutes of Health

Disease-causing changes or mutations found only in the sperm of the father could predict the risk of autism in children.

A team of scientists, led by researchers from the University of California (UC) San Diego School of Medicine tested the sperm of fathers who were already parents of children with an autism spectrum disorder (ASD). They found that the disease-causing mutations were present in up to 15% of the fathers sperm cells -- information that could not be determined through other means such as blood samples.

The causes of autism spectrum disorder (ASD) in children are not fully understood, and researchers believe that both genetics and the environment have a role to play. In some cases, the disorder is linked to mutations that appear only in the child and are not inherited from either parents DNA.

Clinicians continue to face an ever-increasing incidence of autism spectrum disorders, without effective strategies available to prevent disease or counsel families.

Recent studies suggest gene-damaging spontaneous mutations are involved in at least 10% to 30% of ASD cases. Researchers believe that the number of mutations increases with the fathers age at time of conception. Such mutations occur spontaneously in parents sperm or eggs or during fertilization. When a disease-causing mutation occurs for the first time in a family, the probability that it could happen again in a future child is not known. Thus, families must make a decision with a great deal of uncertainty, say experts.

According to the researchers, they have developed a method to measure disease-causing mutations found only in the sperm of the father and assess chances the mutations will cause disease. The team says the new method -- described in Nature Medicine -- provide expectant parents with a more accurate assessment of autism risk in future children.

Autism afflicts 1 in 59 children and we know that a significant portion is caused by de novo (spontaneous) DNA mutations, yet we are still blind to when and where these mutations will occur, says Dr. Jonathan Sebat, professor and chief of the Beyster Center for Molecular Genomics of Neuropsychiatric Diseases at UC San Diego School of Medicine, in the analysis.

With our new study, we can trace some of these mutations back to the father, and we can directly assess the risk of these same mutations occurring again in future children, says Dr. Sebat, a co-senior author of the study.

The US Centers for Disease Control and Prevention (CDC) describes autism spectrum disorder as a developmental disability that can cause significant social, communication and behavioral challenges. For 2014, the overall prevalence of ASD in the US was estimated at 16.8 per 1,000 (one in 59) children aged 8 years.

There are likely many causes for multiple types of ASD. There may be many different factors that make a child more likely to have an ASD, including environmental, biologic and genetic factors. Most scientists agree that genes are one of the risk factors that can make a person more likely to develop this disorder, says CDC.

For their study, the researchers analyzed the sperm of eight fathers of autistic children. The objective, says the team, was to look for the presence of multiple, genetically different sets of cells in the same person, a condition called mosaicism.

While medical textbooks teach us that every cell in the body has an identical copy of DNA, this is fundamentally not correct. Mutations occur every time a cell divides, so no two cells in the body are genetically identical, says first author Dr. Martin Breuss, an assistant project scientist in the lab of Dr. Joseph Gleeson, also a co-senior study author.

The researchers explain that mosaicism can cause cancer or can be silent in the body. If a mutation occurs early in development, then it will be shared by many cells within the body. But if a mutation happens just in sperm, then it can show up in a future child, but not cause any disease in the father, says Breuss.

The researchers used a technique called deep whole-genome sequencing. They found genetic variants in the children that were matched only in the fathers sperm.

Previously research by the team, says Dr. Gleeson, showed that mosaicism in a child can lead to diseases like epilepsy. Here, we show that mosaicism in one of the parents is at least as important when thinking about genetic counseling, says Dr. Gleeson, professor of neuroscience at UC San Diego School of Medicine and director of neuroscience research at the Rady Childrens Institute for Genomic Medicine.

The researchers said that if the study is developed into a clinical test, fathers could have their sperm studied to determine their precise risk of recurrence in future children. The method might also be applied to men who have not had children yet, but who want to know the risk of having a child with a disease, says the team.

Continued here:
Mutations in a fathers sperm could predict the risk of autism in children: Study - MEAWW

Filmmaker and actor Xavier Dolan and the co-founders of the Montreal International Jazz Festival, Andr Mnard and Alain Simard, were among those who were inducted into the Order of Canada on Friday. Legendary Quebec actor Marcel Sabourin, 84, was named an Officer of the Order.

Artists, former politicians, scientists and community leaders were recognized for their extraordinary contributions. A total of 120 people were either appointed to the Order or received promotions.

Former prime minister Stephen Harper and former ambassador Raymond Chrtien received the highest rank of Companion to the Order.

Mnard and Simard were appointed Officers Mnard for his contribution to the Montreal cultural scene, notably as artistic director of the (jazz festival), Simard for his key role in positioning Montreal as a city of festivals and for his leadership as the head of quipe Spectra.

Among the other new Officers of the Order are four-time Olympic womens hockey gold medallist Caroline Ouellette and former Quebec cabinet minister Raymond Bachand.

Denyse McCann, a co-founder of quipe Spectra, was selected as a Member of the Order. Dolan received the same honour for his talent, which has earned him international recognition as an actor, screenwriter and director. Gilles Ste-Croix was also appointed as a Member for his creativity and imagination as co-founder and director of the Cirque du Soleil.

In the university and scientific sector, UQAM professor Alain-G. Gagnon (Officer) was recognized for his contribution to the social sciences, notably for his research into federalism, francophone-anglophone relations, and national identities.

McGill University Professor Daniel Jutras (Officer), was honoured for his contributions to the development of pluralist law internationally and for his contributions as a lawyer, professor and university administrator.

CHUM researcher Pavel Hamet (Member), was recognized for his contributions to genetic medicine and to the development of new clinical treatments for hypertension and diabetes.

Jean-Charles Coutu, the former mayor of Rouyn-Noranda (Officer), was praised for his contributions to the legal profession in the area of Indigenous justice and for his community involvement.

Elsewhere in Canada, biologist Anne Dagg, known as the queen of giraffes, became a Member of the Order for her contributions to the modern scientific understanding of the giraffe.

Dagg was one of several women honoured by the Order for their scientific work, including 2018 Nobel Prize winner Donna Strickland (Companion) and Noni MacDonald of Halifax (Officer), a pediatrician who has served on behalf of the World Health Organization.

Other Montrealers named to the Order:

Officers

Annette av Paul, for her contributions to ballet and for her mentorship as a dancer, teacher and director.

Karen Messing, for her pioneering research into ergonomic work conditions, particularly as they affect womens health.

Members

Maurice Brisson, for his expertise in designing electrification plans and for his philanthropic contributions to electrical engineering education.

Marie Gigure, for her leadership in commercial and corporate law, for her commitment to increasing the role of women in business, and for her dedication to the community.

Arshavir Gundjian, for his contributions to recognizing and promoting Armenian culture in Canada and abroad.

Alcides Lanza, for his decades-long contributions to the contemporary music scene and for championing Canadian music here and abroad.

Isabelle Marcoux, for promoting diversity within Quebecs economic community and for her involvement in numerous fundraising campaigns.

Robert Dick Richmond, for his innovative designs as an aeronautical engineer and for his contributions to the aviation industry.

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Xavier Dolan, Andr Mnard and Alain Simard appointed to the Order of Canada - Montreal Gazette

Scientists adding human brain genes to monkeys its the kind of thing youd see in a movie like Rise of the Planet of the Apes. But Chinese researchers have done just that, improving the short-term memories of the monkeys in a study published in March in the Chinese journal National Science Review. While some experts downplayed the effects as minor, concerns linger over where the research may lead.

The goal of the work, led by geneticist Bing Su of Kunming Institute of Zoology, was to investigate how a gene linked to brain size, MCPH1, might contribute to the evolution of the organ in humans. All primates have some variation of this gene. However, compared with other primates, our brains are larger, more advanced and slower to develop; the researchers wondered whether differences that evolved in the human version of MCPH1 might explain our more complex brains.

Su and his team injected 11 rhesus macaque embryos with a virus carrying the human version of MCPH1. The brains of the transgenic monkeys those with the human gene developed at a slower pace, akin to that of a human, than those in transgene-free monkeys. And by the time they were 2 to 3 years old, the transgenic monkeys performed better and answered faster on short-term memory tests involving matching colors and shapes. However, there werent any differences in brain size or any other behaviors.

But the results arent what has the scientific community buzzing. Some individuals question the ethics of inserting a human brain gene into a monkey an action Rebecca Walker, a bioethicist at the University of North Carolina, argues could be the start of a slippery slope toward imbuing animals with humanlike intelligence. In a 2010 paper, James Sikela, a geneticist at the University of Colorado School of Medicine, and coauthors asked whether a humanized monkey would fit into its society, or would live in inhumane conditions due to its altered genes.

To justify the work, Su and his co- authors suggested that it could provide insights into neurodegenerative and social disorders but they dont describe what those applications might be. I dont really see anything in the paper that would make me think that [the experiment] was necessarily a good idea, says Walker.

Su declined Discovers request for comment, but said in an article for China Daily, Scientists agree that monkey models are at times irreplaceable for basic research, especially in studying human physiology, cognition and disease. And in the research paper, the authors contend that the relatively large phylogenetic distance (about 25 million years of divergence from humans) alleviates ethical concerns. (Rhesus macaques are less like humans in terms of social and cognitive capacities than primates such as chimpanzees, which are more closely related to us.) This greater evolutionary distance suggests it would be harder to wind up with a macaque that acts like a human.

But that reasoning falls flat for Walker. It doesnt really matter when they became differentiated from humans on the phylogenetic tree, she says. Theyre talking about improved short-term memory, which would be putting them sort of closer to us in terms of those cognitive abilities. She thinks manipulating these skills makes the work ethically dubious and requires stronger justification.

While monkeys and humans have similar genomes, Su said in the China Daily article, there are still tens of millions of genetic differences. Changing one gene carefully designed for research will not result in drastic change.

Sikela agrees that such a change may be minor. Still, he wonders about the possibility of finding a gene with a large effect on cognition.

Theres some risky elements to going down this road, Sikela says. One needs to think about the consequences of where this is leading and whats the best way to study these kinds of questions.

Walker also worries about where this work leads. Could we enhance human brains through these methods? she asks. While she thinks were nowhere close to that yet, she notes that science can advance surprisingly quickly. For instance, CRISPR the gene-editing technique that once seemed far removed from human research was used in China to edit the genomes of twins in 2018. (See our No. 11 story of the year, page 32.)

It does feel worrisome to be doing this research in primates, Walker says. And then potentially thinking about how that could be used in humans.

[This story originally appeared in print as "Researchers React to Human Genes in Monkeys."]

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Scientists Put a Human Intelligence Gene Into a Monkey. Other Scientists are Concerned. - Discover Magazine

Its been a banner year for First Opinion. We published nearly 500 essays written by more than 600 authors from industry, academia, government, and private life in the United States and beyond. They took on the mundane, like the implications of the Elijah E. Cummings Lower Drug Costs Now Act (aka H.R. 3), and the fanciful, like why we need a Public Domain Day to highlight when drugs go off patent.

Authors addressed the opioid crisis, patent thickets, the personal toll imposed by drug shortages, drug costs, deaths of despair, the oxymoron of having a waiting room in an emergency department, shoddy production of generic drugs by foreign manufacturers, the burgeoning use of artificial intelligence and machine learning in new drug research and development and health care, and much, much more.

Here are the five most widely read First Opinions of 2019. If you didnt get to read them when they first appeared, now is as good a time as any:

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1. 23andMe had devastating news about my health. I wish a person had delivered it Dorothy Pomerantz thought it would be fun to have her DNA analyzed, so she sent her spit to 23andMe. A link in an email took her to the companys website, where she learned she was at very high risk of developing breast and ovarian cancer. Im not the first person to get surprising and terrible news from an at-home genetic testing company. With the increasing popularity of 23andMe, and other companies like it, I wont be the last. But she wished she had gotten the news from a person.

2. Time in range: a new way for people with diabetes to monitor blood sugar More and more people with diabetes are using continuous glucose meters, which measure blood sugar every few minutes. That information offers a new way to evaluate how well someone is controlling his or her diabetes: time in range. The University of Washingtons Dr. Lorena Alarcon-Casas Wright explains how it works.

3. Our child received a devastating diagnosis before she was born. We decided to protect her Allison Chang learned that, at 15 weeks of gestation, her daughter had severe malformations due to trisomy 18, a deadly genetic condition. She and her husband could not protect our daughter from trisomy 18, but we could shield her from any pain or agony that would come with it.

4. I have spinal muscular atrophy. Critics of the $2 million new gene therapy are missing the point Nathan Yates has lived with spinal muscular atrophy for all 30 years of his life. He answers critics upset over the $2.1 million cost of Zolgensma, a new drug to treat the condition, and asks them to take into account its long-term benefits.

5. Ghost networks of psychiatrists make money for insurance companies but hinder patients access to care When Jack Turban started his training to become a psychiatrist, he went looking for a therapist of his own. What he found were ghost networks of mental health providers.

And heres a bonus: Published in July 2018, the essay Physicians arent burning out. Theyre suffering from moral injury was the third most widely read First Opinion of 2019.

On to 2020!

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5 most widely read First Opinions of 2019 - STAT

Illustration by Andy Potts

Say goodbye to insulin injections and hello to snake toxins.

From penicillin to 3D-printed kidneys, the medical field has long served as a major catalyst of human ingenuity. In Colorado, that innovation doesnt appear to be slowing down. Centennial State institutions are helping pioneer treatments that could revolutionize health careboth today and in the years ahead.

A Gilded PillAbout 416,000 adults in Colorado suffer from diabetes. No wonder, then, that oral insulin (read: no more needles) is considered the holy grail of diabetes care. Denvers Creekside Endocrine Associates is part of the quest as one of only 37 places in the country testing an insulin pill developed by New Yorks Oramed Pharmaceutical. The key is ensuring the capsule reaches the liver before dissolving in stomach acid. If successful, the pill could also drastically lower the average cost of diabetes care, which is currently nearly $10,000 a year in the United States.

Conversation StarterThis past August, UCHealth introduced the world to Alexas nerdy cousin, Livi. An artificial-intelligence-based virtual assistant, Livi can be summoned on an Amazon Echo by saying Alexa, ask UCHealth. Users can then pepper her with commands like Email me information on Crohns disease or Find me a neurologist, and Livi will consult network sources to locate the information. UCHealth hopes to expand Livis capabilities over the next few years. This fall, for example, she was integrated into its electronic medical record system and mobile app so she can check your test results and appointment times.

Game TheoryIn 2017, Childrens Hospital Colorado unveiled one of the first full-time hospital gaming and technology departments in the world. Patients with movement-debilitating illnesses such as cerebral palsy get the much-needed, potentially dexterity-improving activity they require by donning virtual reality and augmented reality headsets and, for example, exploring alien planets. The diversions can also make it easier for kids to undergo difficult treatments: The anxiety a child feels before a lumbar puncturean injection of medicine into her spinal fluidmight be lessened if she can confront the procedure while wielding a lightsaber.

Snake Venom SalesmanA professor at the University of Northern Colorado might have finally found a way for serpents to pay penance for the whole exile-from-Eden thing: Stephen Mackessys Venom Analysis Lab, which launched in the mid-1990s, has shown that toxins from some venomous snakes are capable of preventing cancer cells from metastasizing. The next step (likely still years away) is finding an application method that would weaponize compounds in the venom against a humans cancer without harming the humans body.

Good GenesBoth Lutheran Medical Center and Kaiser Permanente are early practitioners of pharmacogenomicsbasically, how your DNA affects your bodys reactions to medicines. In Lutherans pilot program, primary care providers give some patients the option of a 20-second cheek swab. Pharmacists and doctors can use subsequent genetic-testing reports to provide recommendations, such as lowering a dosage because genetic traits reveal your body might absorb drugs faster or suggesting you avoid a particular medication.

This article appeared in the 2020 issue of 5280 Health.

Excerpt from:
The Innovations That Will Revolutionize Health Care in Colorado - 5280 | The Denver Magazine

P. Todd Stukenberg, PhD, of UVAs Department of Biochemistry and Molecular Genetics and the UVA Cancer Center, works in his lab. Credit: Dan Addison | UVA

Scientists at the University of Virginia School of Medicine have discovered a strange new organelle inside our cells that helps to prevent cancer by ensuring that genetic material is sorted correctly as cells divide.

The researchers have connected problems with the organelle to a subset of breast cancer tumors that make lots of mistakes when segregating chromosomes. Excitingly, they found their analysis offered a new way for doctors to sort patient tumors as they choose therapies. They hope these insights will allow doctors to better personalize treatments to best benefit patients sparing up to 40 percent of patients with breast cancer, for example, a taxing treatment that wont be effective.

Some percentage of women get chemotherapy drugs for breast cancer that are not very effective. They are poisoned, in pain and their hair falls out, so if it isnt curing their disease, then thats tragic, said researcher P. Todd Stukenberg, PhD, of UVAs Department of Biochemistry and Molecular Genetics and the UVA Cancer Center. One of our goals is to develop new tests to determine whether a patient will respond to a chemotherapeutic treatment, so they can find an effective treatment right away.

The organelle Stukenberg and his team have discovered is essential but ephemeral. It forms only when needed to ensure chromosomes are sorted correctly and disappears when its work is done. Thats one reason scientists havent discovered it before now. Another reason is its mind-bending nature: Stukenberg likens it to a droplet of liquid that condenses within other liquid. That was the big wow moment, when I saw that on the microscope, he said.

These droplets act as mixing bowls, concentrating certain cellular ingredients to allow biochemical reactions to occur in a specific location. Whats exciting is that cells have this new organelle and certain things will be recruited into it and other things will be excluded, Stukenberg said. The cells enrich things inside the droplet and, all of a sudden, new biochemical reactions appear only in that location. Its amazing.

P. Todd Stukenberg, PhD, of UVAs Department of Biochemistry and Molecular Genetics and the UVA Cancer Center, discovered an unknown organelle in our cells that helps ensure genetic material is sorted correctly when cells divide. Credit: Dan Addison | UVA

Its tempting to think of the droplet like oil in water, but its really the opposite of that. Oil is hydrophobic it repels water. This new organelle, however, is more sophisticated. Its more of a gel, where cellular components can still go in and out but it contains binding sites that concentrate a small set of the cells contents, Stukenberg explained. Our data suggests this concentration of proteins is really important. I can get complex biochemical reactions to occur inside a droplet that Ive been failing to reconstitute in a test tube for years. This is the secret sauce Ive been missing.

While its been known for about eight years that cells make such droplets for other processes, but it was unknown that they make them on chromosomes during cell division. Stukenberg believes these droplets are very common and more important than previously realized. I think this is a general paradigm, he said. Cells are using these non-membranous organelles to regulate much of their work.

In addition to helping us understand mitosis how cells divide Stukenbergs new discovery also sheds light on cancer and how it occurs. The organelles main function is to fix mistakes in tiny microtubules that pull apart chromosomes when cells are dividing. That ensures each cell winds up with the correct genetic material. In cancer, though, this repair process is defective, which can drive cancer cells to get more aggressive.

He has also developed tests to measure the amount of chromosome mis-segregation in tumors, and he hopes that this might allow doctors to pick the proper treatment to give cancer patients. We have a way to identify the tumors where the cells are mis-segregating chromosomes at a higher rate, he said. My hope is to identify the patients where treatments such as paclitaxel are going to the most effective.

Having looked at breast cancer already, he next plans to examine the strange organelles role in colorectal cancer.

###

Stukenberg and his colleagues have described their discovery in the scientific journal Nature Cell Biology. The research team consisted of Prasad Trivedi, Francesco Palomba, Ewa Niedzialkowska, Michelle A. Digman, Enrico Gratton and Stukenberg.

Reference: The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex by Prasad Trivedi, Francesco Palomba, Ewa Niedzialkowska, Michelle A. Digman, Enrico Gratton and P. Todd Stukenberg, 3 September 2019, Nature Cell Biology.DOI: 10.1038/s41556-019-0376-4

The research was supported by the National Institutes of Health, grants R01GM124042, R24OD023697 and P41-GM103540; and the National Science Foundation, grant MCB-1615701.

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Strange New Organelle That Helps Prevent Cancer Discovered in Our Cells - SciTechDaily

As the old saying goes, strike when the iron is hot. That's what a new gene editing start-up named Beam Therapeutics hopes to do by conducting an initial public offering (IPO) less than two years after forming and more than a year before it asks regulators for permission to begin clinical trials. Given the excitement over genetic medicines, it might be wise to take advantage of the open window now.

Assuming the IPO proceeds as planned, Beam Therapeutics will offer investors a second chance to own a next-generation gene editing technology platform and the first next-generation CRISPR tool. Here's why investors might want to keep the business on their radar.

Image source: Getty Images.

Beam Therapeutics bears some similarities to Editas Medicine (NASDAQ:EDIT). Both trace their origins back to the Broad Institute in Boston. They share a trio of all-star scientific founders: Dr. Feng Zhang, Dr. David Liu, and Dr. Keith Joung. Each company's technology platform is built on CRISPR-based tools.

But the differences are more important for investors. Editas Medicine is developing gene editing tools that require Cas enzymes to cut both strands of DNA. While that theoretically provides the ability to delete or insert genetic sequences to treat diseases, the approach relies on innate DNA repair mechanisms. When the built-in safeguards on those mechanisms break down, cells can turn cancerous. CRISPR-CasX tools can also create unintended genetic edits, and have a relatively low efficiency.

Beam Therapeutics is developing gene editing tools based on a new technique called base editing. The enzymatic approach doesn't make double-stranded breaks in DNA. Instead, it induces chemical reactions to change the sequence of the genetic alphabet -- A (adenine), T (thymine), C (cytosine), and G (guanine) -- one letter at a time. Base editing can make A-to-G edits, C-to-T edits, G-to-A edits, and T-to-C edits.

The next-generation approach decouples CRISPR gene editing tools and the need to make double-stranded breaks in DNA, which is the most pressing concern facing Editas Medicine, CRISPR Therapeutics (NASDAQ:CRSP), and Intellia Therapeutics (NASDAQ:NTLA).

Clinical Consideration

CRISPR-CasX Gene Editing

CRISPR Base Editing

Does it cut DNA?

Yes, enzymatically cuts both strands of DNA

No

Can be used to insert new genetic material into a sequence?

Yes

No, but it can enzymatically change an existing DNA sequence

Does it trigger DNA repair mechanisms?

Yes

No

Source: Beam Therapeutics, author.

While base editing can't make every possible edit (example: A-to-T edits), it can target a number of disease-driving genetic errors. And Beam Therapeutics has inked important collaboration deals to augment the capabilities of its technology platform:

After reviewing the details, investors see that there's a tangled web of related transactions that all flow back to the Broad Institute, which is going to great lengths to extract every ounce of value from its scientific discoveries. Similar actions have caused a stir in the scientific community in recent years. If the profit-seeking terms of the non-profit research institution's agreements are too strict, then it may pose a risk to Beam Therapeutics at the expense of investors.

Image source: Getty Images.

Investors familiar with gene editing stocks will immediately recognize the programs included in the pipeline of the base editing pioneer. The lead assets take aim at blood disorders, and are part of a push to engineer better immunotherapies to treat cancer.

In beta thalassemia and sickle cell disease, Beam Therapeutics is first attempting to increase the production of fetal hemoglobin, which confers natural immunity to both conditions. That's similar to the lead drug candidate of CRISPR Therapeutics, which recently demonstrated promising results from the first two patients in a phase 1 clinical trial.

A second program in sickle cell disease aims to directly correct the genetic mutation responsible for the blood disorder. It involves changing a single base -- perfectly suited for base editing.

In immunotherapy, Beam Therapeutics is working to engineer better chimeric antigen receptor T (CAR-T) cells that can be used as cellular medicines to treat various types of cancers. CRISPR Therapeutics, Editas Medicine, and Intellia Therapeutics are deploying CRISPR gene editing in the same applications, while Precision BioSciences (NASDAQ:DTIL) is leaning on ARCUS gene editing to do the same. The latter's lead drug candidates are in immunotherapy, a unique distinction among gene editing stocks.

Beam Therapeutics' pipeline also includes a range of potential assets aimed at gene correction, gene silencing, and more complex editing, but none have entered clinical trials. The company doesn't expect to file investigational new drug (IND) applications -- required for regulators to sign off on the start of clinical trials -- until 2021. But since the window for an IPO might be slammed shut by then, the business is exploring a market debut now.

There aren't many details in the company's S1 filing concerning a potential date for a market debut or how much money the company is aiming to raise. The filing says $100 million, but that's just a placeholder for the initial submission. The actual amount will be determined once Wall Street gets an idea of the level of interest in an IPO, which will determine the number of shares to offer and the price.

Assuming the IPO takes place, Beam Therapeutics and base editing offer investors a technological upgrade over the first-generation gene editing platforms leaning on CRISPR-CasX tools. The next-generation tools aren't perfect, and there are risks related to the agreements with the Broad Institute and sister start-ups, but this is certainly a gene editing stock worth watching.

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This Start-up Might Be the Next Gene Editing IPO - The Motley Fool

A group led by researchers at Baylor College of Medicine has identified significant differences at the epigenetic level the chemical tags in DNA that help regulate gene expression between two clinically distinct forms of acute childhood malnutrition known as edematous severe acute malnutrition (ESAM) and non-edematous SAM (NESAM).

The researchers report in the journal Nature Communications that ESAM, but not NESAM, is characterized by a reduction in methyl chemical tags in DNA and complex changes in gene activity, including both enhanced and reduced gene expression. Some of the genes that lost their methyl tags have been linked to other disorders of nutrition and metabolism, such as abnormal blood sugar and fatty liver disease, conditions that also have been observed in ESAM. The findings support consideration of methyl-group supplementation in ESAM.

Severe acute childhood malnutrition presents in two clinically distinct forms: ESAM and NESAM, said corresponding author Dr. Neil Hanchard, assistant professor of molecular and human genetics and the USDA/ARS Children's Nutrition Research Center at Baylor. ESAM is characterized by body swelling and extensive dysfunction of multiple organs, including liver, blood cells and the gut, as well as skin and hair abnormalities. NESAM, on the other hand, typically presents with weight loss and wasting.

The differences between ESAM and NESAM are still not fully explained despite decades of studies addressing this question. In the current study, Hanchard and his colleagues looked to better understand the conditions by investigating whether there were differences at the molecular level, specifically on DNA methylation.

The decision to look at DNA methylation was partly driven by previous studies looking at biochemical markers in these individuals. In particular, the turnover of a particular amino acid called methionine, said Hanchard.

Previous work has shown that methionine turnover is slower in ESAM than in NESAM. Methionine is a central ingredient of 1-carbon metabolism, a metabolic pathway that is key to DNA methylation. Lower methionine turnover suggested the possibility of alterations in DNA methylation.

First, we conducted a genome-wide analysis of DNA methylation. When we found in children acutely ill with ESAM genes with levels of DNA methylation that were significantly different from those in NESAM patients, the levels were always lower. Of the genes analyzed, 161 showed a highly significant reduced level of methylation in ESAM, when compared to the same genes in NESAM, Hanchard said.

Interestingly, a group of adults who had recovered from having ESAM malnutrition in their childhood did not show the same reduction in DNA methylation the researchers observed in childhood acute cases. This suggested that lower DNA methylation was probably related to acute ESAM.

Knowing that DNA methylation helps regulate gene expression, Hanchard and his colleagues next investigated whether there were differences in gene expression between ESAM and NESAM. They found that reduced overall methylation in ESAM resulted in a complex pattern of gene expression changes. For some genes, having reduced methylation enhanced their expression, while for others it reduced it.

Among the genes that were highly affected by reduced methylation were some of those related to conditions such as blood sugar regulation, fatty liver disease and other metabolic problems, which are also commonly seen more often in ESAM than NESAM.

Our findings contribute to a better understanding of the molecular events that likely result in the differences between ESAM and NESAM, Hanchard said. Although we still dont know why malnutrition leads to ESAM in some children, while it results in NESAM in others, our findings suggest that, once ESAM gets on its way, methylation changes are likely involved in the clinical signs and symptoms of the condition. There is also evidence that individual genetic variation also influences the level of DNA methylation. Furthermore, I am excited about the possibility that altering the molecular outcome of malnutrition with specific interventions could one day help alter the clinical outcome.

Other contributors to this work include first author Katharina V. Schulze, Shanker Swaminathan, Sharon Howell, Aarti Jajoo, Natasha C. Lie, Orgen Brown, Roa Sadat, Nancy Hall, Liang Zhao, Kwesi Marshall, Thaddaeus May, Marvin E. Reid, Carolyn Taylor-Bryan, Xueqing Wang, John W. Belmont, Yongtao Guan, Mark J. Manary, Indi Trehan and Colin A. McKenzie.

See a complete list of author affiliations and financial support for this study.

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Form of severe malnutrition linked to DNA modification - Baylor College of Medicine News

Dr. Lu Qi is director of the Tulane University Obesity Research Center at Tulane School of Public Health and Tropical Medicine.

Getting a good nights sleep could be beneficial for long-term health. A pioneering new study led by Dr. Lu Qi, director of the Tulane University Obesity Research Center, found that even if people had a high genetic risk of heart disease or stroke, healthy sleep patterns could help offset that risk. The study is published in the European Heart Journal.

The researchers looked at genetic variations known as SNPs (single nucleotide polymorphisms) that were already known to be linked to the development of heart disease and stroke. They analysed the SNPs from blood samples taken from more than 385,000 healthy participants in the UK Biobank project and used them to create a genetic risk score to determine whether the participants were at high, intermediate or low risk of cardiovascular problems.

The researchers followed the participants for an average of 8.5 years, during which time there were 7,280 cases of heart disease or stroke.

We found that compared to those with an unhealthy sleep pattern, participants with good sleeping habits had a 35% reduced risk of cardiovascular disease and a 34% reduced risk of both heart disease and stroke, Qi says. Researchers say those with the healthiest sleep patterns slept 7 to 8 hours a night, without insomnia, snoring or daytime drowsiness.

When the researchers looked at the combined effect of sleep habits and genetic susceptibility on cardiovascular disease, they found that participants with both a high genetic risk and a poor sleep pattern had a more than 2.5-fold greater risk of heart disease and a 1.5-fold greater risk of stroke compared to those with a low genetic risk and a healthy sleep pattern. This meant that there were 11 more cases of heart disease and five more cases of stroke per 1,000 people a year among poor sleepers with a high genetic risk compared to good sleepers with a low genetic risk. However, a healthy sleep pattern compensated slightly for a high genetic risk, with just over a two-fold increased risk for these people.

A person with a high genetic risk but a healthy sleep pattern had a 2.1-fold greater risk of heart disease and a 1.3-fold greater risk of stroke compared to someone with a low genetic risk and a good sleep pattern. While someone with a low genetic risk, but an unhealthy sleep pattern had 1.7-fold greater risk of heart disease and a 1.6-fold greater risk of stroke.

As with other findings from observational studies, our results indicate an association, not a causal relation, Qi says. However, these findings may motivate other investigations and, at least, suggest that it is essential to consider overall sleep behaviors when considering a persons risk of heart disease or stroke.

Read more here:
Can good sleep patterns offset genetic susceptibility to heart disease and stroke? - News from Tulane

In the world of rare diseases, patient testimonies about the extreme difficulties of receiving an accurate diagnosis for an illness are numerous. For instance, one woman, sick for most of her young life, was not properly diagnosed with idiopathic gastroparesis an ultra-rare disease that affects stomach motility and digestion until late in college after seeing numerous different specialists in multiple fields and undergoing a battery of testing.1 Another patient, now active in the rare disease advocacy community, went undiagnosed with familial partial lipodystrophy a disease that, among other things, causes selective fatty tissue loss for 37 years.2

Unfortunately, these stories are not unique. One survey indicated that it took on average 7.6 years to properly diagnose a rare disease patient in the United States.3 Another study indicated that a rare disease patient on average consulted eight different physicians before landing on an accurate diagnosis, with only 12.9 percent of respondents indicating that they had seen only one physician prior to diagnosis (23.5 percent of respondents had seen between six and 10 physicians).4 Frequently, rare disease patients exhibit similar symptoms as other, more common diseases, making diagnosis complicated and leaving patients confused and frustrated about a path forward. Further complicating the situation is that traditional treatments for more common illnesses that mimic rare disease symptoms, such as irritable bowel syndrome in the case of the aforementioned gastroparesis patient, may actually worsen a patient's condition.

As such, the misdiagnosis of rare diseases, in addition to being traumatic for patients and their families, can be extremely expensive. One study indicated that over a 10-year period, an undiagnosed rare disease patient cost over 100 percent more than the average patient. This was due in part to a significant increase in outpatient visits compared with the average patient. (The cost differential was heightened in pediatric patients.)5 Such data indicates that shortening the path to diagnosis for rare disease patients may lead not only to increase patient health but also to a significant reduction in overall long-term healthcare costs.

According to the National Institutes of Health (NIH), there may be upward of 7,000 rare diseases in the United States affecting as many as 30 million people, or nearly one-tenth of the U.S. population.6 Alarmingly, only 5 percent of identified rare diseases have an approved treatment. Despite this daunting figure, approximately 80 percent of rare diseases have genetic origins, a common factor that points to genetic (the testing of individual variants or individual/multiple genes and their effects on an individual) and genomic (the study through various methods of an individual's entire genome and its interaction with the environment) testing as logical tools for identifying and ultimately combating these illnesses.

Genetic Testing Becoming More Common

From concept to execution, the Human Genome Project at the NIH took approximately 15 years and involved the creation of the National Center for Human Genome Research (now the National Human Genome Research Institute, an official Institute at NIH), the collaboration of hundreds of national and international scientists, and an approximate, inflation-adjusted total investment of $5 billion.7,8Since that time, the cost of performing genetic and genomic testing has declined significantly, with a per-genome cost of slightly less than $1,000 in 2019 compared with per-genome costs of approximately $95 million and $30,000 in 2001 and 2010, respectively.9 This significant cost reduction, which has been associated with the development of next-generation sequencing platforms and leaps in computer hardware development, among other things, has opened the door for patients to more readily access these important resources.

Most tests fall into overall categories of DNA diagnostic testing that include single-gene tests, which can detect an abnormality in a gene associated with a particular genetic illness; whole exome sequencing, which sequences the protein-encoding regions of genes; or whole genome sequencing, which is the most rigorous in that it involves sequencing the individual's entire genome. Given the sheer number of rare diseases and the size of the human genome, it is not surprising that there are numerous genetic tests on the market today. One study indicated that there are approximately 75,000 genetic tests on the market, or 10 issued every day.10

However, insurance coverage for these technologies is minimal and inconsistent despite recent positive reception for the increased use of enhanced technologies for patient treatment through the Precision Medicine Initiative, the NIH's Cancer Moonshot and similar programs. One study indicated that coverage for multigene testing varied drastically by disease type and that tests for broad indications or a large range of genes (i.e., those tests that may be helpful in narrowing down disease possibilities in a diagnostic profile) are frequently not covered by insurers.11 It should be noted that some progress has been made on national coverage determinations for some more widely recognized testing technologies. For instance, next-generation sequencing, a revolutionary sequencing technology that sequences genetic material multiple times simultaneously against a reference genome, received a reissued national coverage determination under the Medicare program from the Centers for Medicare & Medicaid Services (CMS) in October 2019.12 However, while this decision was significant as a model for future coverage for genetic testing services, it was only a minor first step in that it was limited only to previously untested patients with ovarian or breast cancer who are Medicare eligible.13

The large and complicated landscape of genetic testing is partially responsible for the lack of insurance coverage for these technologies. For instance, there are only about 200 standardized Current Procedural Terminology (CPT) codes to identify various types of genetic tests to insurers, other physicians, hospitals and health systems, limiting the ability for payers to systematically cover these technologies. This is especially true when applying "medical necessity criteria," which requires a provider to submit accurate information showing that a treatment or test is medically necessary to treat or diagnose a specific illness in order for it to be reimbursed by a payer. Data have shown that a majority of spending in the past several years on genetic tests has gone to noninvasive prenatal tests, cancer screening tests and multiple-gene analyses.14 This is unsurprising given that some of these technologies target pre-identified, validated markers and that newer screening methods present fewer risks for patients than other, more traditional or invasive testing methods.15 For many conditions, however, showing the medical necessity of genetic testing is still a complicated and unpredictable process when a patient is in the middle or beginning of his or her diagnostic odyssey.

Thus, coverage of new genetic testing technologies continues to remain a major challenge for the medical community and a mystery for the tens of millions of U.S. patients with rare diseases. Although small-scale studies and other evidence show that the use of genetic testing as a means to more quickly and accurately diagnose patients can reduce overall health expenditures, policymakers still lack systematic data showing the effectiveness of genetic testing as a means of cutting overall health spending at a macro level.

Help on the Horizon?

Bills have been introduced as recently as the 116th Congress that would create demonstration projects to test coverage of genetic testing technologies for certain patients to help inform future expansions of genetic testing coverage. In addition, Reps. Diana DeGette (D-Colo.) and Fred Upton (R-Mich.), the original champions of the 21st Century Cures Act,16 recently issued a request for information to help inform a follow-on version of the landmark legislation dubbed "Cures 2.0."17 One of the main focuses of their inquiry is into "how Medicare coding, coverage, and payment could better support patients' access to innovative therapies." Expanded coverage to increase access to genetic testing technologies could certainly fit within this scope and would help supplement expanded access and coverage of other new and innovative healthcare technologies for rare disease patients.

Stakeholders across the rare disease landscape have also shared consistent concerns with the length of time between when a new or breakthrough medical technology is approved and when it receives coverage by insurers. Underutilized programs may help speed new technologies to the patients that need them by shortening the gap between approval and coverage. One such example is the U.S. Food and Drug Administration (FDA)-CMS parallel review program for medical devices, which was recently touted by U.S. Department of Health and Human Services (HHS) Deputy Secretary Eric Hargan at the recent FDA/CMS Summit18 and through which a next-generation sequencing test received a parallel approval and coverage determination in 2017.19 These efforts may help the scientific community and others assemble data about how greater access to these technologies positively affect patient care, provide information necessary for lawmakers to empower CMS, the FDA and others to work together on increasing coverage and access, as well as to create mechanisms to speed new technologies to patients in need.

In addition to testing expansion of coverage and access for genetic and genomic testing, further investments should be made into public-private partnerships and other information gathering networks that may centralize information from a diverse group of medical professionals to provide patients additional resources for rare disease diagnosis. For instance, the Undiagnosed Diseases Network, housed at the NIH, utilizes a dozen sites nationwide where teams of physicians assess rare disease patients and share data, including genetic testing data through a "sequencing core," to maximize the amount of national expertise available to pin down rare disease diagnoses that would be extremely difficult and expensive to receive if patients sought expertise individually.20 In addition to further investment in these resources, continued policy development and investment in the development of artificial intelligence technologies and diagnostic support software tools, which have shown promise in assisting physicians in the early detection of rare disease through symptom analysis,21 will provide additional means for patients to receive care more quickly through largely noninvasive means.

Finally, payers both public and private may lack expertise in understanding and evaluating genetic tests, especially for rare diseases. Insurers should prioritize hiring individuals to supplement their teams who have some form of advanced knowledge not only of rare diseases but also the nature of genetic testing technologies and how they are used to expedite disease diagnoses. This is especially true given the rapid development of new testing systems and the growing use of other diagnostic technologies promoted in part by provisions in the 21st Century Cures Act and other legislation.

While it typically refers to something that is uncommon, the term "rare" can also imply heightened value. Greater investment in improving the diagnostic odyssey for rare disease patients, including through greater coverage of new technologies, can only enhance the value and efficiency of the U.S. healthcare system for all patients not just the few.

Read more:
Sequence of Events: Genetic Testing Offers Significant Promise, But Coverage and Access Limited - Lexology

By Michael Erman

NEW YORK (Reuters) Novartis is in discussion with patient groups over its lottery-style free drug program for its multi-million-dollar gene therapy for spinal muscular atrophy (SMA) after criticism that the process could be unfair to some babies with the deadly disease.

The company said on Friday that it will be open to refining the process in the future, but it is not making any changes at this time. The program is for patients in countries where the medicine, called Zolgensma, is not yet approved for the rare genetic disorder, which can lead to death and profound physical disabilities.

At $2.1 million per patient, Zolgensma is the worlds costliest single-dose treatment.

Novartis said the program will open for submission on Jan. 2 and the first allocation of drugs would begin in February. Novartiss AveXis unit, which developed the drug, will give out 50 doses of the treatment through June for babies under 2 years old, it said on Thursday, with up to 100 total doses to be distributed through 2020.

Patient advocacy group SMA Europe had a conference call with the company on Friday, according to Kacper Rucinski, a board member of the patient and research group who was on the call.

There are a lot of ethical questions, a lot of design questions that need to be addresses. We will be trying to address them in January, Rucinski said. He said the program has no method of prioritizing who needs the treatment most, calling it a Russian roulette.

The company said it developed the plan with the help of bioethicists with an eye toward fairness.

This may feel like youre blindly passing it out, but it may be the best we can do, said Alan Regenberg, who is on the faculty at Johns Hopkins Berman Institute of Bioethics and was not among the bioethicists Novartis consulted with on the decision. It may be impossible to separate people on the basis of prognosis out of the pool of kids under 2, he said.

According to Rucinski, the parties will continue their discussion in January to see what can be improved in the design of the program.

Novartis said on Thursday that because of manufacturing constraints it is focused on providing treatment to countries where the medicine is approved or pending approval. It has one licensed U.S. facility, with two plants due to come on line in 2020.

Zolgensma, hit by turmoil including data manipulation allegations and suspension of a trial over safety concerns, is the second SMA treatment, after Biogens Spinraza.

Not all of the SMA community are opposed to Novartis program.

Rajdeep Patgiri moved from the United Kingdom to the United States in April so his daughter could receive Zolgensma. She has responded well to the treatment, and Patgiri worries that negative attention to the program could keep patients from receiving the drug.

The best outcome for all patients would be if everybody could get the treatment. Given all the constraints, a lottery is probably the fairest way to determine who receives the treatment, he said.

(Reporting by Michael Erman; Additional reporting by John Miller in Zurich; Editing by Leslie Adler)

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