StemCell Therapy

Diabetes Mellitus is a disease that involves impaired glucose metabolism. Sudden adverse changes in blood glucose (high or low) can lead to altered mental status, to seizures, and even death. Long-term complications include damage to end organs, such as eyes, kidneys, heart, and the neurological system.

Further, this is a condition that would renderan existing medical certificate invalid from the moment the pilot knew of the diagnosis, regardless of any theoretical period of validity that might appear to remain for that certificate.

Are all pilots with diabetes grounded indefinitely? Is there any hope for a pilot with diabetes to fly again? What about commercially?

The answers are reassuring. Private pilots with well-controlled diabeteshave been flying for many years. And a recently implemented program with the support of the Federal Air Surgeon will now enable even more diabetics to return to commercial flying.

Without going into an elaborate explanation of itsphysiology, lets break diabetes down into two categories: non-insulin-dependent and insulin-dependent.

Insulin is a hormone that is released by the pancreas in response to blood glucose levels. All body tissues use glucose for energy. When blood glucose rises, the pancreas secretes insulin, permitting the bodily tissues to store and use glucose for various metabolic functions.

In certain cases of diabetes, the production of insulin is significantly decreased or completely absent. Common names include juvenile, type 1, or insulin-dependent diabetes (IDDM). Dont let the term juvenile confuse the situation, as there are times when insulin dependence might not occur until well into adulthood.

The relevant premise here is that the body has stopped producing sufficient insulin to regulate blood glucose, regardless of the persons age. You might also see the term insulin-treated diabetes (ITDM) in various publications, and for the purposes of FAA medical certification, IDDM and ITDM can be used synonymously.

In other cases, the bodily tissues have become resistant to the insulin that the pancreas is dutifully producing (obesity is a common cause of insulin resistance). Terms familiar to most people include adult-onset, type 2, or non-insulin-dependent diabetes.

Google mellitus for the amusing reference of how that word became part of the lore of diabetes centuries ago. I will provide more pathophysiologic information when I discuss the individual types of diabetes and the respective FAA certification programs more specifically in future submissions.

Therefore, I wont go into the formalities and minutia of how to diagnose, treat, and monitor diabetes in this discussion. Suffice it to say that poorly-controlled diabetes poses a significant threat to aviation safety, not to mention long-term health.

Diabetes that can be controlled with diet, exercise, and weight loss is the proverbial no-brainer in FAA medical certification. Anything a pilot can do without medical intervention is always preferable for long-term health maintenance.

All classes of medical certificates can be easily obtained in this setting and usually a special issuance is not required (at times this is followed through a slightly amended protocol for pre-diabetes that Ill discuss at a future date).

The necessity for oral and some of the injectable non-insulin medications that lower blood glucose to control diabetes also does not preclude FAA medical certification. In this case, while the pilot will be followed under a special issuance authorization, all classes of medical certificates are again included in this protocol. I have had many pilots flying commercially on first- and second-class medical certificates for many years who are taking oral diabetic medications.

If a pilot requires insulin, however, things change. Before 1996, any insulin-dependent pilot was unable to fly (all classes of medical certificates were excluded). Beginning in 1996, pilots could obtain a third-class FAA medical certificate if they are taking insulin and their diabetes is well controlled.

Fortunately, the program for third-class IDDM pilots has been a great success. The very rare adverse in-flight incidents over the years with diabetic pilots usually have occurred in pilots with poorly controlled diabetes who likely would not havebeen granted a special issuance authorization in the first place.

A pilot who requires insulin for treatment has been excluded for classes of FAA medical certificates higher than third-class until just recently. I have been a vocal advocate to the FAA and its various Federal Air Surgeons over the years that well-controlled IDDM pilots should be considered for first- and second-class certification.

With the current precise continuous glucose monitoring (CGM) electronics and advancements available, an insulin-dependent diabetic is now able to maintain tightly-controlled blood glucose levels.

In 2002, Canada began permitting IDDM pilots to fly commercially in a multi-pilot crew environment. The UK began doing so in 2012, and now the U.S. joined that group last month (on November 7).

Notably, there is no restriction in the FAA protocol that an IDDM pilot must be in a crew environment. Thus, an FAA-licensed pilot with a special issuance for IDDM can fly single-pilot so long as all provisions are met. The FARs dont permit the FAA to put restrictions such as must be part of a multi-pilot crew on first-class medical certificates.

There are also several other countries that permit private flying in pilots with various forms of diabetes.

As you can imagine, the FAA was very cautious and reviewed the advances in diabetic management technologies methodically over many years before authorizing this new program. No different than any other special issuance program, the FAA did not want aviation accidents resulting from a poorly conceived program.

This would, of course, be a tragedy for anyone involved in the accident and could jeopardize the entire program itself. Out of respect for caution, the FAA spent many years working on this program. And now, its finally here!

However, the requirements are probably the most extensive of any special issuance program that we have. There will be ongoing evaluations of numerous organ systems. In addition to using the latest technology to monitor and treat a pilot's diabetes, evaluations will be ongoing for eyes, heart, kidneys, and neurological systems.

The data presentation to the FAA is also extensive and thorough. As with some of the other special issuance conditions, the FAA has developed comprehensive checklistsfor pilots, their AMEs, and the treating physiciansand flow sheets to assist in the detailed data presentation to the FAA. Ongoing CGM data will also be required.

As exhaustive as this program is, it has finally opened the world of commercial flying to IDDM pilots who require a first- or second-class FAA medical certificate. I am hopeful that the program will be as successful as the earlier program for third-class pilots has been.

Those with IDDM are often some of the most motivated pilots there are, and the new gadgetry involved has demonstrated to the FAA that precise control of diabetes can indeed be achieved and, therefore, such pilots do not pose a threat to aviation safety. Thus, it is predicted that IDDM pilots will be able to fly safely in commercial operationson first- and second-class special issuance authorizationsin the U.S.

For a pilot to obtain a special issuance authorization under this new IDDM protocol, they will need an organized and motivated team of support. The pilot, first and foremost, must adequately control their diabetes using modern electronics, including CGM devices, as that also will improve the likelihood of maintaining long-term health.

Next, the treating physician must be willing to complete thorough FAA flow sheets and, at select times, consulting physicians will have to provide evaluation data of the other organ systems mentioned above. Finally, the AME must be willing to choreograph all of the data into a packet that will be acceptable to the FAA.

Read more:
AINsight: Diabetes and Flying | Business Aviation - Aviation International News

There are an estimated 30.3 million people with diabetes in the United States, with approximately 7.2 million individuals not aware they have the disease.

Uncontrolled diabetes poses a major threat to vital organs and other body tissues, which heal more slowly because of the disease.

Diabetes is the inability to manufacture or properly use insulin, impairing the bodys ability to regulate sugar (glucose) levels which provide energy to cells and tissues throughout the body. Therefore, it is a disease that affects many parts of the body and is associated with serious complications such as heart disease, stroke, blindness, kidney failure and lower limb amputations. The leading cause of hospitalization among people with diabetes is foot ulcers and infections, but most of those problems are largely preventable.

More than 60 percent of all nontraumatic lower-limb amputations worldwide are related to complications from the disease, according to the American Diabetes Association. For that reason, the Michigan Podiatric Medical Association (MPMA) has tips to help diabetic patients take better care of their feet.

While is it extremely important for those with diabetes to receive regular foot exams by a podiatrist, keeping feet healthy to remain active can often prevent one from developing Type 2 diabetes, says Jodie Sengstock, DPM, MPMA director of professional relations. Our feet are our foundation. Keeping them healthy improves quality of life.

While there is no cure for diabetes, patients can live with it well. A person with diabetes may enjoy a full and active life with proper diet, exercise, medical care and careful management at home.

Managing and treating the disease requires a team of specialists including a primary care physician, endocrinologist, ophthalmologist, dentist, vascular surgeon and podiatrist.

Podiatrists are trained to treat foot conditions that can be caused by diabetes, such as: neuropathy, infection and ulcers.

While ulcers open sores are the most common diabetes-related foot problem, several others are also serious and prevalent, including neuropathy (pain or numbness), skin changes, poor circulation and infection. The nerve damage that diabetes causes may mean a person with an ulcer or injury may be unaware of it until it becomes infected. Regular care from a podiatrist can reduce amputation rates up to 80 percent, according to research of the American Podiatric Medical Association.

Here are some tips for home management:

People with diabetes should inspect their feet daily and look vigilantly for signs of ulcers, including irritation, redness, cracked or dry skin especially around the heels or body fluid, such as blood, on their socks.

Discuss diabetes and the risks with family members. Diabetes can be hereditary, so talk to family members about monitoring blood sugar and foot health.

Never go barefoot. Always protect feet with the proper footwear and make sure socks and shoes are comfortable and fit well.

Trim toenails straight across, and never cut the cuticles. Seek immediate treatment for ingrown toenails, as they can lead to serious infection.

Never try to remove calluses, corns or warts by yourself. Over-the-counter products can burn the skin and cause irreparable damage to the foot.

Exercise. Walking can keep weight down and improve circulation. Be sure to wear appropriate athletic shoes.

Keep feet elevated while sitting.

Wear thick, soft socks. Avoid socks with seams, which can rub and cause blisters or other skin injuries.

Have new shoes properly measured and fitted. Foot size and shape often changes over time. Shoes that fit properly should not rub or cause irritation.

Wiggle toes and move feet and ankles up and down for five-minute sessions throughout the day.

Visit an MPMA podiatrist regularly at least two times per year to avoid unnecessary complications.

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Your feet need special treatment when you have diabetes - The Oakland Press

BUSAN, SOUTH KOREA Whether cardiovascular disease risk reduction efforts should be more aggressive in women than men with the diabetes depends on how you interpret the data.

Two experts came to differentconclusions on this question during a heated, but jovial, debate last week here at the International Diabetes Federation 2019 Congress.

Endocrinologist David Simmons, MB BChir, Western Sydney University, Campbelltown, Australia, argued that diabetes erases the well-described life expectancy advantage of 4-7 years that women experience over men in the general population.

He also highlighted the fact that the heightened risk is of particular concern in both younger women and those with prior gestational diabetes.

But Timothy Davis, BMedSc MB BS, DPhil, an endocrinologist and general physician at Fremantle Hospital, Western Australia, countered that the data only show the diabetes-attributable excess cardiovascular risk is higher among women than men, but that the absolute risk is actually greater in men.

Moreover, he argued, at least in type 1 diabetes, there's no evidence that more aggressive cardiovascular risk factor management improves outcomes.

Simmons began by pointing out that although, on average, women die at an older age than men, it has been known for over 40 years that this "female protection" is lost among insulin-treated women, particularly as a result of their increased risk for cardiovascular disease.

In a 2015 meta-analysis of 26 studies, women with type 1 diabetes were found to have about a 37% greater risk of all-cause mortality compared to men with the condition when mortality is contrasted with that of the general population, and twice the risk of both fatal and nonfatal vascular events.

The risk appeared to be greater among women who were younger at the time of diabetes diagnosis. "This is a really important point the time we would want to intervene," Simmons said.

In another meta-analysis of 30 studies including 2,307,694 individuals with type 2 diabetes and 252,491 deaths, the pooled women-to-men ratio of the standardized mortality ratio for all-cause mortality was 1.14.

In those with versus without type 2 diabetes, the pooled standardized mortality ratio in women was 2.30 and in men was 1.94, both significant compared to those without diabetes.

And in a 2006 meta-analysis of 22 studies involving individuals with type 2 diabetes, the pooled data showed a 46% excess relative risk using standardized mortality ratios in women versus men for fatal coronary artery disease.

Meanwhile, in a 2018 meta-analysis of 68 studies involving nearly 1 million adults examining differences in occlusive vascular disease, after controlling for major vascular risk factors, diabetes roughly doubled the risk for occlusive vascular mortality among men (relative risk, 2.10), but tripled it among women (3.00).

Women with diabetes aged 35-59 years had the highest relative risk for death over follow-up across all age and sex groups: they had 5.5 times the excess risk compared to those without diabetes, while the excess risk for men of that age was 2.3-fold.

"So very clearly, it's these young women who are most at risk, "emphasized Simmons, whois an investigator for Novo Nordisk and a speaker for Medtronic, Novo Nordisk, and Sanofi.

The question has arisen whether the female/male differences might be because of differences in cardiovascular risk factor management, Simmons noted.

A 2015 American Heart Association (AHA) statement laid out the evidence for lower prescribing of statins, aspirin, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors among women compared with men, Simmons said.

And some studies suggest medication adherence is lower in women than men.

In terms of medications, fenofibrate appears to produce better outcomes in women than men, but there is no evidence of gender differences in the effects of statins, ACE inhibitors, or aspirin, Simmons said.

He also outlined the results of a 2008 study of 78,254 patients with acute myocardial infarction from 420 US hospitals in 2001-2006.

Women were older, had more comorbidities, less often presented with ST-elevation myocardial infarction (STEMI), and had a higher rate of unadjusted in-hospital death (8.2% vs 5.7%; P < .0001) than men. Of the partcipants, 33% of women had diabetes compared with 28% of men.

The in-hospital mortality difference disappeared after multivariable adjustment, but women with STEMI still had higher adjusted mortality rates than men.

"The underuse of evidence-based treatments and delayed reperfusion among women represent potential opportunities for reducing sex disparities in care and outcome after acute myocardial infarction," the authors concluded.

"It's very clear amongst our cardiology colleagues that something needs to be done and that we need more aggressive cardiological risk reduction in women," Simmons said.

"The AHA has already decided this. It's already a policy. So why are we having this debate?" he wondered.

He also pointed out that women with prior gestational diabetes are an exceptionally high-risk group, with a two-fold excess risk for cardiovascular disease within the first 10 years postpartum.

"We need to do something about this particularly high-risk group, independent of debates about gender," Simmons emphasized. "Clearly, women with diabetes warrant more aggressive cardiovascular risk reduction than men with diabetes, especially at those younger ages," he concluded.

Davis began his counter argument by stating that estimation of absolute vascular risk is an established part of strategies to prevent cardiovascular disease, including in diabetes.

And that risk, he stressed, is actually higher in men.

"Male sex is a consistent adverse risk factor in cardiovascular disease event prediction equations in type 2 diabetes. Identifying absolute risk is important," he said, noting risk calculators include male sex, such as the risk engine derived from the United Kingdom Prospective Diabetes Trial.

And in the Australian population-based Fremantle study, of which Davis is an author, the absolute 5-year incidence rates for all outcomes including myocardial infarction, stroke, heart failure, lower extremity amputation, cardiovascular mortality, and all-cause mortality were consistently higher in men versus women in the first phase, which began in the 1990s and included 1426 individuals with diabetes (91% had type 2 diabetes).

In the ongoing second phase, which began in 2008 with 1732 participants, overall rates of those outcomes are lower and the discrepancy between men and women has narrowed, Davis noted.

Overall, the Fremantle study data "suggest that women with type 2 diabetes do not need more aggressive cardiovascular reduction than men with type 2 diabetes because they are not at increased absolute vascular risk," he stressed.

And in a "sensitivity analysis" of two areas in Finland, the authors concluded that the stronger effect of type 2 diabetes on the risk of CHD in women compared with men was in part explained by a heavier risk factor burden and a greater effect of blood pressure and atherogenic dyslipidemia in women with diabetes, he explained.

The Finnish authors wrote, "In terms of absolute risk of CHD death or a major CHD event, diabetes almost completely abolished the female protection from CHD."

But, Davis emphasized, rates were not higher in females.

So then, "Why is there the view that women with type 2 diabetes need more aggressive cardiovascular risk reduction than men with diabetes?"

"It probably comes back to confusion based on absolute risk versus a comparison of relative risk within each sex," he asserted.

Lastly, in a meta-analysis published just in July this year involving more than 5 million participants, compared to men with diabetes, women with diabetes had a 58% and 13% greater risk of CHD and all-cause mortality, respectively.

"This points to an urgent need to develop sex- and gender-specific risk assessment strategies and therapeutic interventions that target diabetes management in the context of CHD prevention," the authors concluded.

But, Davis noted, "It is not absolute vascular risk. It's a relative risk compared across the two genders. In the paper, there is no mention of absolute vascular risk."

"Greater CVD mortality in women with and without diabetes, versus men, doesn't mean there's also an absolute vascular increase in women versus men with diabetes," he said.

Moreover, Davis pointed out that in an editorial accompanying the 2015 meta-analysis in type 1 diabetes, Simmons had actually stated that absolute mortality rates are highest in men.

"I don't know what happened to his epidemiology knowledge in the last 4 years but it seems to have gone backwards," he joked to his debate opponent.

And, Davis asserted, even if there were a higher risk in women with type 1 diabetes, there is no evidence that cardiovascular risk reduction measures affect endpoints in that patient population. Only about 8% of people with diabetes in statin trials had type 1 diabetes.

Indeed, he noted, in the American Diabetes Association (ADA) Standards of Medical Care in Diabetes 2019, the treatment goals for individual cardiovascular risk factors do not mention gender.

What's more, David said, there is evidence that women are significantly less likely than men to take prescribed statins and are more likely to have an eating disorder and underdose insulin, "suggesting significant issues with compliance...So, trying to get more intensive risk reduction in women may be a challenge."

"Women with diabetes do not need more aggressive cardiovascular risk reduction than men with diabetes, irrespective of type," he concluded.

International Diabetes Federation 2019 Congress. December 5, 2019.

For more diabetes and endocrinology news, follow us on Twitter and Facebook.

Link:
Do Women With Diabetes Need More CVD Risk Reduction Than Men? - Medscape

ANTALYA, Turkey

More people in Turkey are being diagnosed with diabetes compared with previous years, an expert said Sunday.

Speaking to the media, Tugbay Tug, a professor at Ankara Universitys Faculty of Medicine, Department of General Surgery, said the number of people in Turkey with diabetes now accounts for more than 10% of the population compared with 7% five years ago.

Tug underlined that Turkey is the third highest country in Europe in terms of the number of diabetes patients.

About half of the patients with diabetes are losing their feet because of foot wounds, he said.

The mortality rate of patients who have lost one organ is much higher than the mortality rate caused by most lethal cancers, and 50% die within three years, he added.

Tug warned that diabetes should not be ignored.

One out of 10 people in society are diabetes patients and the number of people with diabetes totals more than 8 million in Turkey, he added.

He said 20% of Turkeys population will have diabetes by 2025 if people dont change their dietary habits.

Scientific data shows that one in four diabetes patients suffer foot wounds. We can say that there are at least 2 million diabetic foot patients in Turkey. This number will increase if we dont live healthy.

*Writing by Davut Demircan

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Number of people in Turkey with diabetes rising: expert - Anadolu Agency

Jumana Y Al-Aama,1,2 Hadiah B Al Mahdi,1 Mohammed A Salama,1 Khadija H Bakur,1,2 Amani Alhozali,3 Hala H Mosli,3 Suhad M Bahijri,4 Ahmed Bahieldin,5,6 Lothar Willmitzer,7 Sherif Edris1,5,6

1King Abdulaziz University, Princess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, KSA; 2King Abdulaziz University Faculty of Medicine, Department of Genetic Medicine, Jeddah, KSA; 3King Abdulaziz University, Faculty of Medicine, Department of Endocrinology and Metabolism, Jeddah, KSA; 4King Abdulaziz University, Faculty of Medicine, Department of Clinical Biochemistry, Jeddah, KSA; 5King Abdulaziz University, Faculty of Science, Biological Sciences Department, Jeddah, KSA; 6Ain Shams University, Department of Genetics, Cairo, Egypt; 7Max-Planck-Institut Fr Molekulare Pflanzenphysiologie, Molecular Physiology, Golm, DE, Germany

Correspondence: Sherif Edris; Jumana Y Al-AamaKing Abdulaziz University, Princess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, KSATel +966 593 66 23 84Email seedris@kau.edu.sa; jalama@kau.edu.sa

Background: Type 2 diabetes, or T2D, is a metabolic disease that results in insulin resistance. In the present study, we hypothesize that metabolomic analysis in blood samples of T2D patients sharing the same ethnic background can recover new metabolic biomarkers and pathways that elucidate early diagnosis and predict the incidence of T2D.Methods: The study included 34 T2D patients and 33 healthy volunteers recruited between the years 2012 and 2013; the secondary metabolites were extracted from blood samples and analyzed using HPLC.Results: Principal coordinate analysis and hierarchical clustering patterns for the uncharacterized negatively and positively charged metabolites indicated that samples from healthy individuals and T2D patients were largely separated with only a few exceptions. The inspection of the top 10% secondary metabolites indicated an increase in fucose, tryptophan and choline levels in the T2D patients, while there was a reduction in carnitine, homoserine, allothreonine, serine and betaine as compared to healthy individuals. These metabolites participate mainly in three cross-talking pathways, namely glucagon signaling, glycine, serine and threonine and bile secretion. Reduced level of carnitine in T2D patients is known to participate in the impaired insulin-stimulated glucose utilization, while reduced betaine level in T2D patients is known as a common feature of this metabolic syndrome and can result in the reduced glycine production and the occurrence of insulin resistance. However, reduced levels of serine, homoserine and allothrionine, substrates for glycine production, indicate the depletion of glycine, thus possibly impair insulin sensitivity in T2D patients of the present study.Conclusion: We introduce serine, homoserine and allothrionine as new potential biomarkers of T2D.

Keywords: glucagon signaling, glycine production, bile secretion, insulin sensitivity/resistance

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Detection of Secondary Metabolites as Biomarkers for the Early Diagnos | DMSO - Dove Medical Press

Are you one of the 26 million people who have experienced genetic testing by companies such as 23andMe or Ancestry? These companies promise to reveal what your genes say about your health and ancestry. Genes are, indeed, the instruction book containing the code that makes you a unique human being. This specific code which you inherit from your parents is what makes you, you.

The genetic coding system works amazingly well, but like all systems, occasionally things dont go as planned. You may inherit a gene that increases your chance of developing a health condition and sometimes the code develops an error causing you to have a devastating disease.

If genetic testing is so powerful in analysing and understanding your health, why cant you just as easily have this same genetic information inform your care at the doctors office? To answer this question, lets first look at the field of using genetic information to drive your healthcare (often referred to as precision or personalized medicine).

Across the globe, researchers devote enormous amounts of time and effort to understand how human genes impact health and billions of dollars are invested. The knowledge of what impact specific genes have on our health has increased tremendously and continues to do so at an amazing pace. Our increased understanding of genes, and how they affect our health, is driving novel methods to halt diseases and new ways of thinking about how medications can be developed to treat diseases.

Precision medicine is a growth area

With all this money and effort being expended, why isnt the use of your genetic information a standard part of your medical care? As the Kaiser Permanente Fellow to the World Economic Forums Precision Medicine Team, I recently had the opportunity to interview leaders from every aspect of Precision Medicine to understand the barriers preventing genetic testing from becoming a standard part of your healthcare.

Those with whom I spoke included insurance companies who pay for the tests, doctors who use and interpret them, genetic counsellors who help you understand test results, diagnostic companies which develop testing, government healthcare regulators, researchers making astonishing discoveries and healthcare organizations who are determining how best to deploy genetic testing.

These interviews suggest that the science behind genetic testing and the knowledge of how genes impact health is far ahead of our ability to make full use of this information in healthcare. Moving genetic testing into your doctors office requires a complex set of technologies, processes, knowledge and payments. Though many of the barriers inhibiting this movement were unique and complex, there were some consistent and common themes:

1. The limited expertise in genetics within healthcare systems. The need for education of healthcare providers as well as the public was regularly highlighted. The use of genetics in healthcare requires specialized knowledge that is outside the expertise of most doctors. Healthcare providers simply dont have time to study this new and rapidly changing information as their hands are full just keeping up with the latest trends and findings in their specialities. Additionally, education on genetics in healthcare is needed for the public. As one person interviewed said: The public watches CSI and thinks the use of DNA and genetics is black and white; using genetics in healthcare is rarely black and white

2. The lack of sufficient genetic counsellors. Genetic counsellors are often used to engage patients prior to testing and after results have been received, providing them with the detailed and nuanced information required for many of these tests. They also support doctors when they need assistance in making decisions about genetic testing and understanding the test results.

3. To successfully embed genetics into your care, doctors need the workflows for genetic testing (receiving results and understanding the impact on their care plans) to become a seamless part of their work. Clinical decision support software for genetics should alert the healthcare provider when genetic testing is merited with a patient, based on information the provider has entered during their examination. The software should then provide a list of appropriate tests and an explanation of why one might be used over another. After doctors order the test, they believe is most appropriate, the system should inform them of the results in clear, easily understandable language. The results should inform the doctor if the care plan for this patient should be modified (with suggestions for how the care should change).

4. Coverage of payments for genetic testing. If such tests are not paid for by insurers or government healthcare agencies (the payers), doctors simply wont order them. In the US and many other countries, there is patchwork coverage for genetic testing. Some tests are covered under specific circumstances, but many are not covered at all. The major reason cited by the payers for not covering genetic testing is a lack of evidence of clinical efficacy. In other words, do these tests provide actionable information, that your doctor can use to ensure better health outcomes? Until the payers see sufficient evidence of clinical efficacy, they will be hesitant to pay for many types of genetic testing. Doctors are concerned about the same thing, according to my research. They want to see the use of these tests in large populations, so they can determine that there is a benefit to using them.

Using your genetic information in healthcare is much more complex than taking a direct-to-consumer genetic test such as those offered by 23andMe. Healthcare is a multifaceted system and doctors already have too much on their plate. As such, there must be sufficient proof that the use of genetic testing will result in better health outcomes for the populations these clinicians serve before it's introduced into this setting.

We cannot hesitate in the face of the above complexities. As I completed the interviews which revealed these barriers, I stumbled across a journal article on this very subject. Written by a prominent group of doctors and researchers from government and leading universities in 2013, it highlights these same barriers and that virtually no progress has been made in the ensuing seven years. This is why I am focusing my fellowship at the World Economic Forum on a new project called Moving Genomics to the Clinic. Taking advantage of the multistakeholder platform of the Forum, the project will quicken the pace of tackling these barriers so that the use of genetic information can become a standard part of your healthcare experience.

License and Republishing

World Economic Forum articles may be republished in accordance with our Terms of Use.

Written by

Arthur Hermann, Fellow, Precision Medicine, World Economic Forum

The views expressed in this article are those of the author alone and not the World Economic Forum.

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How to bring precision medicine into the doctor's office - World Economic Forum

SALT LAKE CITY, Dec. 14, 2019 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in molecular diagnostics and precision medicine, announced that results of a new validation study of the companys polygenic risk score (PRS) for breast cancer were presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Tx. The key finding is that the PRS significantly improves the precision and accuracy of breast cancer risk estimates for women of European ancestry who have pathogenic variants (PV) in high- and moderate-penetrance breast cancer genes.

Our goal is to help women understand their risk of breast cancer so that they can take steps to live longer, healthier lives. Women who have a family history of breast cancer should consider hereditary cancer testing with the myRisk Hereditary Cancer test, said Jerry Lanchbury, Ph.D., chief scientific officer of Myriad Genetics. In this landmark study, we demonstrated that for women who test positive for a mutation in one of the five most common breast cancer genes, there are additional genetic factors called single nucleotide polymorphisms (SNPs) that can further influence their lifetime risk of breast cancer.

A summary of the study follows below. Follow Myriad on Twitter via @myriadgenetics and keep up to date with SABCS meeting news and updates by using the #SACBS19 hashtag.

Myriad Poster Presentation Title: Polygenic Breast Cancer Risk Modification in Carriers of High and Intermediate Risk Gene Mutations.Presenter: Elisha Hughes, Ph.D.Date: Saturday, Dec. 14, 2019, 7:009:00 a.m.Location: Poster P6-08-07

This validation study evaluated the 86-SNP PRS as a breast cancer risk factor for women who carry PV in the BRCA1, BRCA2, CHEK2, ATM and PALB2 genes and for PV-free women. The analysis included data from 152,012 women of European ancestry who received a myRisk Hereditary Cancer test as part of their clinical hereditary cancer risk assessment. The results demonstrated that the 86-SNP PRS significantly modified the breast cancer risk for women with pathogenic mutations in the five tested breast cancer genes (p-value <10-4). For some women, the PRS significantly increased the gene-based risk of breast cancer, while in others the gene-based risk was reduced (see Graph 1). Importantly, the greatest PRS risk-modification was observed in carriers of CHEK2, ATM and PALB2 mutations with some women reaching the risk levels associated with BRCA1 and BRCA2 mutations.

To view Graph 1: PRS Significantly Modifies Lifetime Breast Cancer Risk in Mutation Carriers , please visit the following link: https://www.globenewswire.com/NewsRoom/AttachmentNg/d56c93ca-e00f-452d-b051-6325a578454c

These findings mean that we have the potential to significantly improve the precision of hereditary cancer risk assessment for women who test positive for mutations in the high and intermediate risk breast cancer genes, said Elisha Hughes, Ph.D., lead investigator and director of Bioinformatics at Myriad Genetics. We are optimistic that this additional genetic information can help clinicians more accurately predict the risk of breast cancer and provide the best care for their patients in the future.

Next StepsThe company plans to publish these new data in a peer reviewed medical journal and make the PRS available for U.S. women of European ancestry who test positive for mutations in breast cancer genes. The PRS currently is available as part of myRisk Hereditary Cancer enhanced with riskScore for women of European ancestry who test negative for pathogenic mutations in the breast cancer genes. Specifically, the riskScore test combines the PRS with the Tyrer-Cuzick model to estimate a womans 5-year and lifetime risk for developing breast cancer. The company is committed to making myRisk Hereditary Cancer enhanced with riskScore available to all ethnicities and is developing the test for women of Hispanic and African-American ancestry who test negative. The company is currently conducting the largest ever PRS study in African Americans and will present the data at a future meeting.

Please visit Myriad at booth #113 to learn more about our portfolio of genetic tests for breast cancer. Follow Myriad on Twitter via @myriadgenetics and keep up to date with Symposium news by using the hashtag #SABCS19.

About riskScoreriskScore is a new clinically validated personalized medicine tool that enhances Myriads myRisk Hereditary Cancer test. riskScore helps to further predict a womens lifetime risk of developing breast cancer using clinical risk factors and genetic-markers throughout the genome. The test incorporates data from more than 80 single nucleotide polymorphisms identified through 20 years of genome wide association studies in breast cancer and was validated in our laboratory to predict breast cancer risk in women of European descent. This data is then combined with a best-in-class family and personal history algorithm, the Tyrer-Cuzick model, to provide every patient with individualized breast cancer risk.

About Myriad myRisk Hereditary CancerThe Myriad myRisk Hereditary Cancer test uses an extensive number of sophisticated technologies and proprietary algorithms to evaluate 35 clinically significant genes associated with eight hereditary cancer sites including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma.

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 Company's 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 related to the Companys polygenic risk score and data being featured at the 2019 San Antonio Breast Cancer Symposium being held Dec. 10-14, 2019 in San Antonio, Tx.; the potential to significantly improve the precision of hereditary cancer risk assessment for women who test positive for mutations in the high and intermediate risk breast cancer genes; this additional genetic information helping clinicians more accurately predict the risk of breast cancer and provide the best care for their patients in the future; publishing these new data in a peer reviewed medical journal and making the PRS available for U.S. women of European ancestry who test positive for mutations in breast cancer genes; making myRisk Hereditary Cancer enhanced with riskScore available to all ethnicities and developing the test for women of Hispanic and African-American ancestry who test negative; conducting the largest ever PRS study in African Americans and presenting the data at a future meeting; and the Company's strategic directives under the caption "About Myriad Genetics." These "forward-looking statements" are based on management's 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, such as the Supreme Court decision in the lawsuit brought against us by the Association for Molecular Pathology et al; 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.

Graph 1

PRS Significantly Modifies Lifetime Breast Cancer Risk in Mutation Carriers

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Myriad's Polygenic Risk Score Personalizes Risk of Breast Cancer for Woman with a Genetic Mutation in Important Breast Cancer GenesNew Clinical...

IU School of Medicine 12/13/19

SAN ANTONIOIndiana University School of Medicine researchers have discovered how to predict whether triple negative breast cancer will recur,and whichwomenare likely toremain disease-free. They will present their findingson December 13, 2019,at the San Antonio Breast Cancer Symposium, the most influential gathering of breast cancer researchers and physicians in the world.

Milan Radovich, PhD, andBryan Schneider, MD,discovered that women whose plasmacontained genetic material from a tumor referred to as circulating tumor DNA had only a 56 percent chance of being cancer-free two years following chemotherapy and surgery. Patients who did not have circulating tumor DNA, or ctDNA,in their plasma had an 81 percent chance that the cancer would not return after the same amount of time.

Triple negative breast cancer is one of the most aggressive and deadliest types of breast cancer because it lacks common traits used to diagnose and treat most other breast cancers. Developing cures for the disease is a priority of theIU Precision Health Initiative Grand Challenge.

The study also examined the impact of circulating tumor cells,or CTCs,which arelive tumor cells that are released from tumors somewhere in the body and float in the blood.

What we found is that if patientswerenegative for bothctDNA and CTC, 90 percent of the women with triple negative breast cancer remained cancer-free after two years, said Radovich, who is lead author of this study and associate professor of surgery and medicalandmolecular genetics at IU School of Medicine.

Advocates for breast cancer researchsaythey are excited to hear about these results.

The implications of this discovery will change the lives of thousands of breast cancer patients, saidNadia E.Miller,who is a breast cancer survivor andpresident of Pink-4-Ever, which is a breast cancer advocacy group in Indianapolis. This is a huge leap toward more favorable outcomes and interventions for triple negative breast cancer patients. To provide physicians with more information to improve the lives of somany is encouraging!

Radovich and Schneider are researchers in theIndiana University Melvin and Bren Simon Cancer Centerand theVera Bradley Foundation Center for Breast Cancer Research. They lead the Precision Health Initiatives triple negative breast cancer team.

The researchers, along with colleagues from theHoosier Cancer Research Network, analyzed plasma samples taken from the blood of 142 women with triple negative breast cancer who had undergone chemotherapy prior to surgery. Utilizing theFoundationOne Liquid Test, circulating tumor DNA was identified in 90 of the women;52 were negative.

The women were participants inBRE12-158,a clinical study that testedgenomically directed therapyversus treatment of the physicians choicein patients withstageI,II or IIItriple negative breast cancer.

Detection of circulatingtumorDNA was also associated with poor overall survival. Specifically, the study showed that patients withcirculatingtumorDNA were four times more likely to die from the disease when compared to those who tested negative for it.

The authors say the next step is a new clinical study expected to begin in early 2020, which utilizes this discovery to enroll patients who are at high risk for recurrence and evaluates new treatment options for them.

Just telling a patient they are at high risk for reoccurrence isnt overly helpful unless you can act on it, said Schneider, who is senior author of this study and Vera Bradley Professor of Oncologyat IU School of Medicine. Whats more important is the ability to act on that in a way to improve outcomes.

Organizers of theSan Antonio Breast Cancer Symposiumselected the researchto highlight frommore than2,000 scientific submissions.

This study was funded by the Vera Bradley Foundation for Breast Cancerand the Walther Cancer Foundation.It is part of theIndiana University Precision Health InitiativeGrand Challenge.The study was managed by the Hoosier Cancer Research Network and enrolled at 22clinical sites across theUnited States.

To interviewMilan Radovich or Bryan P. Schneideron Friday, Dec. 13,contactChristine Drury at 317-385-9227 (cell)on-site in San Antonio.

Local mediacancontact Anna Carrera in Indianapolisat 614-570-6503 (cell).

For the full media kit, click here.

# # #

What theyre saying:

IU School of Medicine DeanJayL.Hess, MD, PhD, MHSA:While we have made extraordinary progress in treating many types of breast cancer, triple negative disease remains a formidable challenge. We are dedicating substantial expertise and resources to this disease, and this discovery is an important step forward. We will continue to press ahead until we have new therapies to offer women with this most aggressive form of breast cancer.

IU School of Medicine Executive Associate Dean for ResearchAnanthaShekhar, MD, PhD:I could not be more proud of our research team here at IU School of Medicine and the IU Precision Health InitiativeGrand Challenge. A few years ago, I gave the teams the challenge to come up with targeted treatments, cures and preventions for triple negative breast cancer, where there had been none. The findings, announced today, show we are well on our way to achieving these bold goals.

Indiana University Melvin and Bren Simon Cancer Center DirectorPatrick J. Loehrer, MD:Addressing an issue of importance in Indiana and globally, our IU cancer researchers are making novel discoveries that have the real potential to impact women with triple negative breast cancer. This work does not happen in a vacuum, but is a product of team science, which characterizes the fabric of our National Cancer Institute-designated Comprehensive Cancer Center.

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IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

The Precision Health Initiative is IUs big health care solution. Led by the IU School of Medicine, the Precision Health Initiative team is working to prevent and cure diseases through a more precise understanding of the genetic, behavioral, and environmental factors that influence a persons health, with bold goals to cure one cancer and one childhood disease and to prevent one chronic illness and one neurodegenerative disease.

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Indiana University School of Medicine researchers use cutting-edge technology to predict which triple negative breast cancer patients may avoid...

A genetic variant in the gene transthyretin (TTR)which is found in about 3 percent of individuals of African ancestryis a more significant cause of heart failure than previously believed, according to a multi-institution study led by researchers atPenn Medicine. The study also revealed that a disease caused by this genetic variant, called hereditary transthyretin amyloid cardiomyopathy (hATTR-CM), is significantly under-recognized and underdiagnosed.

The findings, which were published inJAMA, are particularly important given the U.S. Food and Drug Administrations approvalof the first therapy (tafamidis) for ATTR-CM in May 2019. Prior to the new therapy, treatment was largely limited to supportive care for heart failure symptoms and, in rare cases, heart transplant.

Our findings suggest that hATTR-CM is a more common cause of heart failure than its perceived to be, and that physicians are not sufficiently considering the diagnosis in certain patients who present with heart failure, says the studys corresponding authorDaniel J. Rader, chair of the Department of Genetics at Penn Medicine. With the recent advances in treatment, its critical to identify patients at risk for the disease and, when appropriate, perform the necessary testing to produce an earlier diagnosis and make the effective therapy available.

Read more at Penn Medicine News.

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This genetic variant is underdiagnosed, under-recognized, and deadly | Penn Today - Penn: Office of University Communications

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Triplet Therapeutics, Inc., a biotechnology company harnessing human genetics to develop treatments for repeat expansion disorders at their source, launched today with $59 million in financing including a $49 million Series A financing led by MPM Capital and Pfizer Ventures U.S. LLC, the venture capital arm of Pfizer Inc. (NYSE: PFE). Atlas Venture, which co-founded and seeded Triplet with a $10 million investment, also participated in the Series A alongside Invus, Partners Innovation Fund and Alexandria Venture Investments.

Triplet was founded in 2018 by Nessan Bermingham, Ph.D., a serial biotech entrepreneur and venture partner at Atlas Venture, along with Atlas Venture and Andrew Fraley, Ph.D., to pursue a transformative approach to developing treatments for repeat expansion disorders, a group of more than 40 known genetic diseases associated with expanded DNA nucleotide repeats. A significant body of human genetic evidence has identified that one central pathway, known as the DNA damage response (DDR) pathway, drives onset and progression of this group of disorders, which include Huntingtons disease, myotonic dystrophy and various spinocerebellar ataxias.

Triplet is developing antisense oligonucleotide (ASO) and small interfering RNA (siRNA) development candidates to precisely knock down key components of the DDR pathway that drive repeat expansion. This approach operates upstream of current approaches in development, targeting the fundamental driver of these diseases. By precisely reducing activity of select DDR targets, Triplets approach is designed to halt onset and progression across a wide range of repeat expansion disorders.

The company has a fully assembled senior management team of industry veterans. Nessan Bermingham, Ph.D., co-founder, president and chief executive officer, has nearly two decades of experience leading life science startups and is a co-founder of Intellia Therapeutics and Korro Bio. Irina Antonijevic, M.D., Ph.D., senior vice president of development, previously led translational medicine and early development at Wave Life Sciences. Brian Bettencourt, Ph.D., senior vice president of computational biology & statistics, comes to Triplet from Translate Bio, where he led modeling and design of oligonucleotide and mRNA therapeutics. David Morrissey, Ph.D., senior vice president of technology, formerly led technology development and delivery of CRISPR/Cas9 gene editing candidates at Intellia Therapeutics. Eric Sullivan, CPA, chief financial officer, brings experience leading financial operations at Gemini Therapeutics and bluebird bio. Jeffrey M. Cerio, Pharm.D., J.D., senior vice president & general counsel, served as senior corporate counsel at Moderna, Inc. before joining the Triplet team.

Were excited to launch Triplet today to transform the treatment of repeat expansion disorders, Dr. Bermingham said. This milestone would not have been possible without the contributions of thousands of patients, whose participation in genetic research has enabled us to build a fundamentally new understanding of the cause of these diseases. With this financing we are positioned to rapidly advance our initial development candidates toward the clinic for patients.

The company will use the Series A funds to progress its first development candidates into IND-enabling studies, as well as to advance natural history studies to inform its clinical development plan and contribute to the scientific understanding of repeat expansion disorders.

More than 40 repeat expansion disorders have been identified, and most of these diseases are severe with limited to no treatment options, said Jean-Franois Formela, M.D., partner at Atlas Venture and Board Chair of Triplet. We have built Triplet to fundamentally transform what has been the treatment strategy for these diseases up to now.

The companys founding Board of Directors is comprised of:

Triplets launch today represents a turning point for the treatment of repeat expansion disorders. I look forward to working with this expert team to develop novel treatments for patients, said Shinichiro Fuse, Ph.D., partner at MPM Capital and member of Triplets Board of Directors.

This group of severe genetic disorders represents an area of high unmet medical need, and we look forward to working with Triplets leadership team as they reimagine the potential treatment paradigm for patients with rare diseases, said Laszlo Kiss, Ph.D., Pfizer Ventures principal and member of Triplets Board of Directors.

Triplet has also formed a Scientific Advisory Board comprised of leading investigators for repeat expansion disorders, including Sarah Tabrizi, Ph.D., professor of clinical neurology at University College London; Jim Gusella, Ph.D., Bullard Professor of Neurogenetics at Harvard Medical School; and Vanessa Wheeler, Ph.D., associate professor of neurology at Massachusetts General Hospital and Harvard Medical School.

About Triplet Therapeutics

Triplet Therapeutics is a biotechnology company developing transformational treatments for patients with unmet medical needs by leveraging insights of human genetics to target the underlying cause of repeat expansion disorders, a group of more than 40 known genetic diseases including Huntingtons disease, myotonic dystrophy and spinocerebellar ataxias. Triplet was founded by Nessan Bermingham, Ph.D., Atlas Venture and Andrew Fraley, Ph.D. Triplet has raised $59 million in funding to date, including its Series A funding in 2019 led by MPM Capital and Pfizer Ventures, with Atlas Venture, Invus, Partners Innovation Fund and Alexandria Venture Investments participating. Triplet is headquartered in Cambridge, Mass. For more information, please visit http://www.triplettx.com.

About Atlas Venture

Atlas Venture is a leading biotech venture capital firm. With the goal of doing well by doing good, we have been building breakthrough biotech startups for over 25 years. We work side by side with exceptional scientists and entrepreneurs to translate high impact science into medicines for patients. Our seed-led venture creation strategy rigorously selects and focuses investment on the most compelling opportunities to build scalable businesses and realize value. For more information, please visit http://www.atlasventure.com.

About MPM Capital

MPM Capital is a healthcare investment firm founding and investing in life sciences companies that seek to cure major diseases by translating scientific innovations into positive clinical outcomes. MPM invests in breakthrough therapeutics, with a focus on oncology. With its experienced and dedicated team of investment professionals, executive partners, entrepreneurs and scientific advisory board members, MPM is powering novel medical breakthroughs that transform patients lives. http://www.mpmcapital.com

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Triplet Therapeutics Launches with $59 Million in Financing to Further its Development of Transformative Treatments for Triplet Repeat Disorders -...

A vector is a microscopic carrier of pieces of DNA. It is used to deliver healthy copies of genes to tissues and organs within patients or deliver the ability to correct the genetic errors. While the technology is moving rapidly, production of vectors is not.

NSW, and in particular the Westmead Precinct, is already at the forefront of international gene therapy research. The aim of this project is to speed up research and translate it into cures for serious genetic diseases affecting children.

The facility will produce vectors to treat illnesses impacting everything from those with life-threatening liver disease to children going blind. Currently the vectors need to imported and its extremely costly to get them to Australia.

Professor Ian Alexander, Head of the Gene Therapy Research Unit at Childrens Medical Research Institute, senior clinician at The Childrens Hospital at Westmead and Professor of Paediatric and Molecular Medicine at the University of Sydney, said the manufacturing facility would be a boost to translation of academic research in NSW.

We see it as the beginning of something much greater, Professor Alexander said.

It is about moving technology into the clinic, which, in future, will benefit many more patients by offering new and better treatment opportunities. This technology could translate into saving the lives of infants with life-threatening conditions.

Dr Leszek Lisowski heads the Translational Vectorology Group at CMRI and is Conjoint Senior Lecturer at the University of Sydney. His team will play a key role in the new facility, through training of staff and developing the manufacturing processes that will underpin operations. In addition, his team specialises in the development of novel vectors optimised for clinical applications targeting liver, eye and many other clinically important organs and tissues.

Dr Lisowski said that this new facility will allow Australian investigators to get around the "bottleneck" of getting vectors from overseas.

The biggest bottleneck that slows down translation of gene therapy tools to the patient is a global lack of vector manufacturing capacity, which significantly extends the timeline and increases the cost of translational studies," he said.

This facility will give Australian researchers prioritised and cost-effective access to clinical gene therapy reagents and will facilitate translation of a large number of exciting preclinical programs from bench to bedside.

The team is excited by this vital investment and looks forward to partnering with government and other funders to enable the facility to achieve its full potential.

The Westmead Precinct is one of the largest health, education, research and training precincts in Australia and a key provider of jobs for the greater Parramatta and western Sydney region. Spanning 75 hectares, the Precinct includes four hospitals, four world-leading medical research institutes, two multidisciplinary university campuses and the largest research-intensive pathology service in NSW.

The University of Sydney has long been a proud partner of the Precinct and is in negotiations about developing a second major campus in the area. By 2050, that campus will include 25,000 students; 1000 staff and researchers; generate $21.7 billion for the NSW economy and support up to 20,000 jobs.

University of Sydney Vice-Chancellor and Principal Dr Michael Spence said that as part of our collaborative work in building a western Sydney global centre of excellence, Precinct partners are growing Australias advanced manufacturing capability.

These developments will strengthen crucial collaborations in the Precinct from R&D and design to distribution in areas such as prevention and wellbeing, biomedical engineering, AI and personalised medicine, Dr Spence said.

Faculty of Medicine and Health Executive Dean Professor Robyn Ward said: This technology will scale up gene therapy using viral vectors from single-condition, life changing successes, for example in spinal muscle atrophy, to a national service.

We are so proud of this leadership at the Westmead Precinct and with our health partners. It is a whole-of-lifespan, true bench-to-clinic approach."

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Here are five things you ought to understand about science, according to professor of genetic medicine Gregg Semenza.

This week, Semenzaalong with William Kaelin Jr. and Peter Ratcliffewill accept the 2019 Nobel Prize in Physiology or Medicine in Stockholm, Sweden, for discovering the gene that controls how cells respond to low oxygen levels.

In the two months since the award was announced, Semenza, director of the vascular program at the Institute for Cell Engineering at Johns Hopkins University, has spoken with audiences around the world about the implications of this work in understanding and eventually treating blood disorders, blinding eye diseases, cancer, diabetes, and other conditions. But hes also spoken about the value of basic science.

Here are five things Semenza says he wishes more people knew about science:

The Nobel Prizes usually go to older scientists for discoveries they made when younger, and because of this, Semenza says people may think that good science is solely the domain of older people.

We often make these findings early in our careers, but it is only much later that the significance of those discoveries becomes apparent, he says.

A lot of science is about taking small steps forward. Big leaps are often the result of collaboration, Semenza says.

For example, when he and his lab identified the HIF-1 gene, which controls cells under low oxygen conditions, they initially ran into problems trying to clone the genes DNApart of the process of learning more about a genes function and other characteristics. He got help from fellow Johns Hopkins scientist Thomas Kelly, who had expertise in a workaround approach: purifying the protein made by HIF-1, which is another way to learn more about the gene and its function in the cell.

There are places with very smart people, and there are places where everybody is friendly, Semenza says. But there are few places with smart people who are almost always willing to help you.

When we wrote the manuscript reporting the discovery of HIF-1, we submitted it to top-tier journals, and they did not find it to be of sufficient interest to warrant publication.

But that didnt stop him: Semenza got help from scientist Victor McKusick, and the Proceedings of the National Academy of Sciences published the paper. It has been cited in more than 6,000 scientific publications.

In high school, I had a biology teacher who inspired me and others to pursue careers in scientific research by teaching us about the scientists and the scientific process that led to discoveries, Semenza says.

She would often preface her description of a scientific discovery by saying, When you win your Nobel Prize, I dont want you to forget that you learned that here. We need to give more emphasis to teachers and reward them for the work that they do, which makes such a difference in the lives of so many.

The inventions and discoveries that come out of basic research are critical for the economy, public health, and treating disease earlier, Semenza says.

It is better, both for patients and for the economy, to treat diseases early rather than later, and we need more research to learn how to more effectively treat many cancers.

Source: Johns Hopkins University

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5 things a Nobel Prize winner wants you to know about science - Futurity: Research News

Though the research was intended as a proof of concept, the experimental gene therapy slowed tumour growth and prolonged survival in mice with gliomas, which constitute about 80% of malignant brain tumours in humans.

The technique takes advantage of exosomes, fluid-filled sacs that cells release as a way to communicate with other cells.

The research was carried out by scientists at the Ohio State University and published in the journal Nature Biomedical Engineering.

While exosomes are gaining ground as biologically friendly carriers of therapeutic materials because there are a lot of them and they dont prompt an immune response the trick with gene therapy is finding a way to fit those comparatively large genetic instructions inside their tiny bodies on a scale that will have a therapeutic effect.

This new method relies on patented technology that prompts donated human cells such as adult stem cells to spit out millions of exosomes that, after being collected and purified, function as nanocarriers containing a drug.

When they are injected into the bloodstream, they know exactly where in the body to find their target even if its in the brain.

Senior study author L. James Lee, professor emeritus of chemical and biomolecular engineering at Ohio State University, said: Think of them like Christmas gifts: the gift is inside a wrapped container that is postage paid and ready to go. This is a Mother Nature-induced therapeutic nanoparticle.

In 2017, Lee and colleagues made waves with news of a regenerative medicine discovery called tissue nanotransfection (TNT). The technique uses a nanotechnology-based chip to deliver biological cargo directly into skin, an action that converts adult cells into any cell type of interest for treatment within a patients own body.

By looking further into the mechanism behind TNTs success, scientists in Lees lab discovered that exosomes were the secret to delivering regenerative goods to tissue far below the skins surface.

The scientists placed about one million donated cells on a nano-engineered silicon wafer and used an electrical stimulus to inject synthetic DNA into the donor cells. As a result of this DNA force-feeding, as Lee described it, the cells need to eject unwanted material as part of DNA transcribed messenger RNA and repair holes that have been poked in their membranes.

The electrical stimulation had a bonus effect of a thousand-fold increase of therapeutic genes in a large number of exosomes released by the cells, a sign that the technology is scalable to produce enough nanoparticles for use in humans.

Essential to any gene therapy is knowing what genes need to be delivered to fix a medical problem. For this work, the researchers chose to test the results on glioma brain tumours by delivering a gene called PTEN, a cancer-suppressor gene. Mutations of PTEN that turn off that suppression role can allow cancer cells to grow unchecked.

For Lee, founder of Ohio States Center for Affordable Nanoengineering of Polymeric Biomedical Devices, producing the gene is the easy part. The synthetic DNA force-fed to donor cells is copied into a new molecule consisting of messenger RNA, which contains the instructions needed to produce a specific protein. Each exosome bubble containing messenger RNA is transformed into a nanoparticle ready for transport, with no blood-brain barrier to worry about.

The testing in mice showed the labelled exosomes were far more likely to travel to the brain tumours and slow their growth compared to substances used as controls.

Because of exosomes safe access to the brain, Lee said, this drug-delivery system has promise for future applications in neurological diseases such as Alzheimers and Parkinsons disease.

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Mother Nature provides new gene therapy strategy to reverse disease - Health Europa

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that the ILLUMINATE-A Phase 3 study of lumasiran, an investigational RNAi therapeutic targeting glycolate oxidase (GO) in development for the treatment of primary hyperoxaluria type 1 (PH1), met its primary efficacy endpoint and all tested secondary endpoints. Specifically, lumasiran met the primary efficacy endpoint of percent change from baseline, relative to placebo, in 24-hour urinary oxalate excretion averaged across months 3 to 6 (p less than 0.0001). The study also achieved statistically significant results for all six tested secondary endpoints (p less than or equal to 0.001). Lumasiran also demonstrated an encouraging safety and tolerability profile. Based on these results, the Company plans to submit a New Drug Application (NDA) and file a Marketing Authorisation Application (MAA) for lumasiran in early 2020.

We are very pleased to report positive topline Phase 3 results for lumasiran, our third wholly owned investigational RNAi therapeutic. Patients living with PH1 and their families are faced with the burden of recurrent and painful stone events and a progressive and unpredictable decline in kidney function that ultimately results in end-stage renal disease and the need for intensive dialysis as a bridge to dual liver/kidney transplantation. The results from ILLUMINATE-A demonstrate that lumasiran can significantly reduce the hepatic production of oxalate, which we believe can thereby address the underlying pathophysiology of PH1, said Akshay Vaishnaw, M.D., Ph.D., President of R&D at Alnylam. Further, we are encouraged by the safety and tolerability profile of lumasiran and believe this investigational medicine has the potential to have a meaningful clinical impact on patients living with PH1. We look forward to submitting regulatory filings in early 2020 and advancing this highly needed medicine one step closer to patients. Finally, we extend our deepest gratitude to the patients, caregivers, investigators, and study staff who participated in ILLUMINATE-A and contributed to what we believe is an important medical advance for the treatment of PH1.

The ILLUMINATE-A results represent a significant landmark for the PH1 patient community. These patients live with the angst of not knowing when that next kidney stone will come or for how long their kidneys will keep working, and they grapple with the possibility of needing new organs. We have lived with the hope that someday patients living with PH1 and their families would finally have a treatment with the potential to have a positive impact on their health and alleviate some of that angst, said Kim Hollander, Executive Director of the Oxalosis and Hyperoxaluria Foundation. Today we are hopeful that we are much closer to that day than we have ever been.

Lumasiran results in ILLUMINATE-A mark our third positive Phase 3 study readout in 2019, positioning Alnylam with the potential for four marketed products by the end of 2020, assuming positive regulatory reviews. We believe this achievement also provides further support of our relatively high product development success rate linked to selection of genetically validated targets and a modular and reproducible platform, said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. With these results in hand, we believe that were on track to exceed our Alnylam 2020 guidance, building by the end of 2020 a global, multi-product, commercial-stage company with a robust portfolio of clinical-stage programs for future growth and an organic product engine for sustainable innovation and patient impact.

ILLUMINATE-A Topline Study ResultsILLUMINATE-A (NCT03681184), a randomized, double-blind, placebo-controlled trial, designed to enroll approximately 30 patients with PH1 ages six and above, at 16 study sites, in eight countries around the world, is the largest interventional study conducted specifically in PH1. Patients were randomized 2:1 to lumasiran or placebo, with lumasiran administered at 3 mg/kg monthly for three months followed by quarterly maintenance doses. The primary endpoint for the study was the percent change from baseline in 24-hour urinary oxalate excretion averaged across months 3 to 6 in patients treated with lumasiran as compared to placebo. At six months, lumasiran met the primary endpoint in patients with PH1 (p less than 0.0001) and achieved statistically significant results for all six hierarchically-tested secondary endpoints (p less than or equal to 0.001), including the proportion of lumasiran patients that achieved near-normalization or normalization of urinary oxalate levels, relative to placebo.

There were no serious or severe adverse events in the study, and results showed that lumasiran was generally well tolerated with an overall profile generally consistent with that observed in Phase 1/2 and open-label extension studies of lumasiran. Lumasiran has received U.S. and EU Orphan Drug Designations, Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA), and a Priority Medicines (PRIME) designation from the European Medicines Agency (EMA). Full ILLUMINATE-A study results will be presented in an oral plenary session on Tuesday, March 31, 2020 at OxalEurope International Congress in Amsterdam, Netherlands.

The Company is also conducting ILLUMINATE-B a global Phase 3 study of lumasiran in PH1 patients less than six years of age, with results expected in mid-2020, and ILLUMINATE-C a global Phase 3 study of lumasiran in PH1 patients of all ages with advanced renal disease, with results expected in 2021.

Conference Call InformationAlnylam Management will discuss the ILLUMINATE-A results via conference call on Tuesday, December 17, 2019 at 8:00 am ET. A webcast presentation will also be available on the Investors page of the Companys website, http://www.alnylam.com. To access the call, please dial 800-239-9838 (domestic) or +1-323-794-2551 (international) five minutes prior to the start time and refer to conference ID 6976021. A replay of the call will be available beginning at 11:00 am ET on the day of the call. To access the replay, please dial 888-203-1112 (domestic) or +1-719-457-0820 (international) and refer to conference ID 6976021.

About LumasiranLumasiran is an investigational, subcutaneously administered RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) in development for the treatment of primary hyperoxaluria type 1 (PH1). HAO1 encodes glycolate oxidase (GO). Thus, by silencing HAO1 and depleting the GO enzyme, lumasiran inhibits production of oxalate the metabolite that directly contributes to the pathophysiology of PH1. Lumasiran utilizes Alnylam's Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology, which enables subcutaneous dosing with increased potency and durability and a wide therapeutic index. Lumasiran has received both U.S. and EU Orphan Drug Designations, a Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA), and a Priority Medicines (PRIME) designation from the European Medicines Agency (EMA). The safety and efficacy of lumasiran have not been evaluated by the FDA, EMA or any other health authority.

About Primary Hyperoxaluria Type 1 (PH1)PH1 is an ultra-rare disease in which excessive oxalate production results in the deposition of calcium oxalate crystals in the kidneys and urinary tract and can lead to the formation of painful and recurrent kidney stones and nephrocalcinosis. Renal damage is caused by a combination of tubular toxicity from oxalate, calcium oxalate deposition in the kidneys, and urinary obstruction by calcium oxalate stones. Compromised kidney function exacerbates the disease as the excess oxalate can no longer be effectively excreted, resulting in subsequent accumulation and crystallization in bones, eyes, skin, and heart, leading to severe illness and death. Current treatment options are very limited and include frequent renal dialysis or combined organ transplantation of liver and kidney, a procedure with high morbidity that is limited due to organ availability. Although a small minority of patients respond to Vitamin B6 therapy, there are no approved pharmaceutical therapies for PH1.

About RNAiRNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as a major scientific breakthrough that happens once every decade or so, and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of todays medicines by potently silencing messenger RNA (mRNA) the genetic precursors that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

About Alnylam PharmaceuticalsAlnylam (Nasdaq: ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust discovery platform. Alnylams commercial RNAi therapeutic products are ONPATTRO (patisiran), approved in the U.S., EU, Canada, Japan, and Switzerland, and GIVLAARI (givosiran), approved in the U.S. Alnylam has a deep pipeline of investigational medicines, including five product candidates that are in late-stage development. Looking forward, Alnylam will continue to execute on its Alnylam 2020 strategy of building a multi-product, commercial-stage biopharmaceutical company with a sustainable pipeline of RNAi-based medicines to address the needs of patients who have limited or inadequate treatment options. Alnylam employs over 1,200 people worldwide and is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit http://www.alnylam.com and engage with us on Twitter at @Alnylam or on LinkedIn.

Alnylam Forward Looking StatementsVarious statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, Alnylam's views with respect to the implications of the positive topline results from the ILLUMINATE-A study and the potential for lumasiran to have a meaningful clinical impact on patients living with PH1, its plans and expected timing for filing applications for regulatory approval of lumasiran, its plans for reporting the full results from the ILLUMINATE-A study, expectations regarding the timing for reporting results from the ILLUMINATE-B and ILLUMINATE-C clinical studies, and expectations regarding the potential to exceed its Alnylam 2020 guidance for the advancement and commercialization of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, Alnylam's ability to discover and develop novel drug candidates and delivery approaches, successfully demonstrate the efficacy and safety of its product candidates, including lumasiran, the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates for a specified indication or at all, actions or advice of regulatory agencies, which may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional pre-clinical and/or clinical testing, delays, interruptions or failures in the manufacture and supply of its product candidates, including lumasiran, obtaining, maintaining and protecting intellectual property, Alnylam's ability to enforce its intellectual property rights against third parties and defend its patent portfolio against challenges from third parties, obtaining and maintaining regulatory approval, pricing and reimbursement for products, including lumasiran, progress in establishing a commercial and ex-United States infrastructure, successfully launching, marketing and selling its approved products globally, Alnylams ability to successfully expand the indication for ONPATTRO in the future, competition from others using technology similar to Alnylam's and others developing products for similar uses, Alnylam's ability to manage its growth and operating expenses, obtain additional funding to support its business activities, and establish and maintain strategic business alliances and new business initiatives, Alnylam's dependence on third parties for development, manufacture and distribution of products, the outcome of litigation, the risk of government investigations, and unexpected expenditures, as well as those risks more fully discussed in the Risk Factors filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

Lumasiran has not been approved by the FDA, EMA, or any other regulatory authority and no conclusions can or should be drawn regarding the safety or effectiveness of this investigational therapeutic.

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Alnylam Reports Positive Topline Results from ILLUMINATE-A Phase 3 Study of Lumasiran for the Treatment of Primary Hyperoxaluria Type 1 - Business...

Parsippany, NJ, Dec. 17, 2019 (GLOBE NEWSWIRE) -- Interpace Biosciences, Inc. (Nasdaq:IDXG) today announced that its Medicare Administrative Contractor (MAC) has issued a new draft local coverage determination (LCD) for the Companys ThyGeNEXT test, representing an increase of approximately $2,400 per assay over previous reimbursement coverage. This increase in reimbursement rates reflects the expansion of the ThyGeNEXT panel to aid in identifying the appropriate patients for surgery. In 2018, Interpace processed approximately 12,500 ThyGeNEXT tests.

Prior to the new LCD code (81455) becoming effective, it was subject to a public comment period, which ended December 15, 2019, and is now subject to an analysis and review period by MACs Medical Directors. Final approval is expected during the first quarter of 2020. ThyGeNEXT has been covered by an existing LCD since it was launched in mid-2018 and its predecessor, ThyGenX, has been covered since 2014.

Jack Stover, President & CEO of Interpace, said, I am very pleased with the draft local coverage announcement and look forward to the final determination, which when approved will demonstrate the quality of our expanded assay, and most importantly supports continued reimbursement for patients and their families potentially affected by Thyroid cancer.

About ThyGeNEXT and ThyraMIR

ThyGeNEXT utilizes state-of-the-art next-generation sequencing (NGS) to identify more than 100 genetic alterations associated with papillary and follicular thyroid carcinomas, the two most common forms of thyroid cancer, as well as Medullary Thyroid Carcinoma. ThyraMIR is the first microRNA gene expression classifier. MicroRNAs are small, non-coding RNAs that bind to messenger RNA and regulate expression of genes involved in human cancers, including every subtype of thyroid cancer. ThyraMIR measures the expression of 10 microRNAs. Both ThyGeNEXT and ThyraMIR are covered by Medicare and Commercial insurers, with more than 280 million members covered.

According to the American Thyroid Association, approximately 20% of the 525,000 thyroid fine needle aspirations (FNAs) performed on an annual basis in the U.S. are indeterminate for malignancy based on standard cytological evaluation, and thus are candidates for ThyGeNEXT and ThyraMIR.

ThyGeNEXT and ThyraMIR reflex testing yields high predictive value in determining the presence and absence of cancer in thyroid nodules. The combination of both tests can improve risk stratification and surgical decision-making when standard cytopathology does not provide a clear diagnosis.

About Interpace Biosciences

Interpace Biosciences is a leader in enabling personalized medicine, offering specialized services along the therapeutic value chain from early diagnosis and prognostic planning to targeted therapeutic applications.

Interpace Diagnostics is a fully integrated commercial and bioinformatics business unit that provides clinically useful molecular diagnostic tests, bioinformatics and pathology services for evaluating risk of cancer by leveraging the latest technology in personalized medicine for improved patient diagnosis and management. Interpace has four commercialized molecular tests and one test in a clinical evaluation process (CEP): PancraGEN for the diagnosis and prognosis of pancreatic cancer from pancreatic cysts; ThyGeNEXT for the diagnosis of thyroid cancer from thyroid nodules utilizing a next generation sequencing assay; ThyraMIR for the diagnosis of thyroid cancer from thyroid nodules utilizing a proprietary gene expression assay; and RespriDX that differentiates lung cancer of primary vs. metastatic origin. In addition, BarreGEN for Barretts Esophagus, is currently in a clinical evaluation program whereby we gather information from physicians using BarreGEN to assist us in positioning the product for full launch, partnering and potentially supporting reimbursement with payers.

Interpace Biopharma provides pharmacogenomics testing, genotyping, biorepository and other customized services to the pharmaceutical and biotech industries. The Biopharma business also advances personalized medicine by partnering with pharmaceutical, academic, and technology leaders to effectively integrate pharmacogenomics into their drug development and clinical trial programs with the goals of delivering safer, more effective drugs to market more quickly, and improving patient care.

For more information, please visit Interpace Biosciences website at http://www.interpace.com.

Forward-looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995, relating to the Company's future financial and operating performance. The Company has attempted to identify forward looking statements by terminology including "believes," "estimates," "anticipates," "expects," "plans," "projects," "intends," "potential," "may," "could," "might," "will," "should," "approximately" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. These statements are based on current expectations, assumptions and uncertainties involving judgments about, among other things, future economic, competitive and market conditions and future business decisions, all of which are difficult or impossible to predict accurately and many of which are beyond the Company's control. These statements also involve known and unknown risks, uncertainties and other factors that may cause the Company's actual results to be materially different from those expressed or implied by any forward-looking statement. Additionally, all forward-looking statements are subject to the Risk Factors detailed from time to time in the Company's most recent Annual Report on Form 10-K and Quarterly Reports on Form 10Q. Because of these and other risks, uncertainties and assumptions, undue reliance should not be placed on these forward-looking statements. In addition, these statements speak only as of the date of this press release and, except as may be required by law, the Company undertakes no obligation to revise or update publicly any forward-looking statements for any reason.

CONTACTS:Investor Relations - Edison GroupJoseph Green(646) 653-7030jgreen@edisongroup.com

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Interpace Biosciences Announces New Draft LCD and Reimbursement for Its Proprietary Thyroid Assay, ThyGeNEXT - GlobeNewswire

Dr Wong Chiang Yin's exposition (The way forward for informed consent in medicine, Dec 14) mentioned the proposals of the workgroup appointed by the Ministry of Health (MOH) to review the taking of informed consent and the Singapore Medical Council disciplinary process. MOH accepted 29 proposals early this month.

I participated in the feedback sessions, during which I submitted my medical and legal viewpoints.

In the field of informed consent, Dr Wong mentioned patient autonomy and patient's interest as cardinal points in the practice of medicine. In informed consent, the patient's right to information and confidentiality may be compromised in only two situations - when the patient is mentally incapacitated, or when the patient has a communicable disease and there is the larger national interest to inform the regulatory authorities.

A third aspect to the right of informed consent has just arisen. This involves the issue of whether doctors have a legal duty to warn patients' relatives of their genetic risks.

Just last month, a legal case was heard in the Royal Courts of Justice in London. The case concerns a man who was diagnosed with an inheritable disease (Huntington's disease). He told his doctors not to reveal this to his daughter, who was then pregnant, fearing that she would terminate her pregnancy. Subsequently, when the disease was manifested in the daughter, she sued the man's doctors on the basis that, if she had known, she would not have continued with her pregnancy.

This case centres on whether doctors should have a legal duty to warn patients' relatives about disease risks from an inherited condition - essentially the balancing act between a duty to protect patient confidentiality versus a duty to warn, and thus prevent harm to relatives.

The case has now gone on appeal to the European Court of Justice and the outcome should be out by the middle of next year. However, empirical data in the UK suggests that there is public support for a legal duty to warn relatives of their genetic risk of disease.

Lim Ee Koon (Dr)

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Forum: Should doctors have legal duty to warn a patient's relatives of genetic risks? - The Straits Times

I'm hesitant to give my child the measles vaccine, because I'm worried about long-lasting side effects. Is it dangerous? Sally G., Jacksonville, Florida

As we've said before, it's smart to get your child the vaccine as early as your pediatrician recommends. The risk of getting vaccinated is greatly outweighed by the benefit of avoiding the measles. For vaccinations overall, the ratio of risk to benefit is one to 40,000. Worldwide, the measles kills over 100,000 children annually. In the U.S., since Jan. 1, there have been 880 cases of the disease, which was declared eradicated here in 2000! The real news, however, is that the re-emergence of measles poses a greater risk than we knew.

Harvard researchers have found that measles causes immune amnesia. It wipes out 20% to 50% of your body's antibodies, which are protecting you from a slew of diseases caused by other viruses and bacteria. That may be why bacterial ear infections and pneumonia are common complications after getting the measles. Long-term effects may be even more serious. And that's another good reason to get your child vaccinated as early as recommended.

So why are so many American parents hesitant? Researchers at Brigham Young University thought it may be because folks don't have firsthand experience with the devastating effects of those illnesses. To test the theory, they sent 250 students out to interview locals who had come down with vaccine-preventable diseases, such as polio, shingles and tuberculosis. Some of those students referred to themselves as "vaccine hesitant," but around 70% became pro-vaccine after learning how life-damaging the diseases were.

Bottom line: Don't make yourself go through firsthand tragedy before you realize how smart it is to get vaccinated! Kids should get the MMR (measles, mumps, rubella) vaccine at 1 year old and again between 28 days later and 6 years old. You can also opt for two doses of the MMRV (measles, mumps, rubella, and varicella/chickenpox) vaccine; it's approved for children 12 months through 12 years old.

Last week I thought I heard someone at the door, but when I checked there was no one there. Am I losing my mind, or should I get my hearing checked? Sam B., Portland, Oregon

If you have ringing in your ears, doorbells or otherwise, you might want to get checked out by an audiologist. It could be a sign of hearing loss. But if it's just a one-time event, it's probably nothing.

Sensory hallucinations what that was are pretty common, and there are many forms. You can hear, see, smell, taste or feel something that isn't there. While they can be associated with serious mental disorders such as schizophrenia, they are also related to certain medications, drug abuse, medical conditions like Parkinson's and perhaps sleep deprivation, stress and anxiety.

They can also result from what Georgetown University neuroscientists say is a bottleneck of feed-forward and feedback signals. It's what can occur when the brain is asked to process more information than it can handle. These days, there is more information out there at your fingertips (coming in and going out) than at any time in human history.

In addition, researchers at Stanford University recently discovered how easy it is to provoke hallucinations. In the lab, they altered the neural activity of mice (those rodents have millions of neurons in their brains; humans have billions) by disrupting about 20 individual neurons using light and sound. When they did so, the mice showed signs of believing something was there when it wasn't. This prompted one researcher to ponder, "Why are we not hallucinating all the time, due to spurious random activity?"

Now, that's not to diminish the seriousness of recurrent hallucinatory episodes that interfere with your everyday quality of life. If that's the case, you should keep a journal of when and where they happen and discuss the incidents with your doctor so he/she can pinpoint the cause.

Mehmet Oz, M.D. is host of "The Dr. Oz Show," and Mike Roizen, M.D. is Chief Wellness Officer and Chair of Wellness Institute at Cleveland Clinic. Email your health and wellness questions to Dr. Oz and Dr. Roizen at youdocsdaily@sharecare.com.

Excerpt from:
Oz & Roizen: Measles wipes out parts of the immune system - Bluffton Today

Food allergens are the scourge of the modern school lunchbox. Many foods contain proteins that can set off an oversized immune reaction and one of the fiercest is the humble peanut.

Around 3% of children in Australia have a peanut allergy, and only 1 in 5 of them can expect to outgrow it. For these unlucky people, even trace amounts of peanut can trigger a fatal allergic reaction.

But what sets the peanut apart from other nuts? Why is it so good at being an allergen?

To answer this, we have to explore the pathway from allergen to allergy, and just what it is about an allergen that triggers a response from the immune system.

Read more: What are allergies and why are we getting more of them?

Before coming into contact with the immune system, an allergen in food needs to overcome a series of obstacles. First it needs to pass through the food manufacturing process, and then survive the chemicals and enzymes of the human gut, as well as cross the physical barrier of the intestinal lining.

After achieving all of this, the allergen must still have the identifying features that trigger the immune system to respond.

Many food allergens successfully achieve this, some better than others. This helps us to understand why some food allergies are worse than others.

The most potent allergens like peanuts have many characteristics that successfully allow them to overcome these challenges, while other nuts display these traits to a lesser extent.

The first characteristic many allergenic foods have, especially peanuts, is strength in numbers. Both tree nuts and peanuts contain multiple different allergens. At last count, cashews contain three allergens, almonds have five, walnuts and hazelnuts have 11 each and peanuts are loaded with no less than 17.

Each allergen has a unique shape, so the immune system recognises each one differently. The more allergens contained in a single food, the higher the potency.Additionally, many of these allergens also have numerous binding sites for both antibodies and specialised immune cells, further increasing their potency.

The first hurdle for a food allergen is the food manufacturing process. Many nuts are roasted prior to consumption. For most foods, heating changes the structure of proteins in a way that destroys the parts that trigger an immune response. This makes them far less potent as allergens.

This is not the case for many tree nuts: allergens in almonds, cashews and hazelnuts survived roasting with no loss of potency.

And for the major peanut allergens, its even worse. Roasting actually makes them more potent.

Read more: Can I prevent food allergies in my kids?

From here, the allergen will have to survive destruction by both stomach acid and digestive enzymes within the human gut. Many nut allergens have the ability to evade digestion to some degree.

Some simply have a robust structure, but peanut allergens actively inhibit some of the digestive enzymes of the gut. This helps them safely reach the small intestine, where the allergens then need to cross the gut lining to have contact with the immune system.

This is where peanut allergens really stand apart from most other allergens. They have the ability to cross the intestinal cells that make up the gut lining. Given their relative sizes, this is like a bus squeezing itself through a cat flap.

Peanut allergens accomplish this remarkable feat by altering the bonds that hold the gut cells together. They can also cross the lining by hijacking the guts own ability to move substances. Once across, the allergens will gain access to the immune system, and from there an allergic response is triggered.

The combination of multiple allergens, numerous immune binding sites, heat stability, digestion stability, enzyme blocking, and the effect on the gut lining makes peanut a truly nasty nut.

This leaves us with a nagging question: if peanuts are so potent, why doesnt everyone develop a peanut allergy? We still dont know.

Recently, a potential vaccine developed by researchers from the University of South Australia has shown promise in reprogramming the immune system of mice and blood taken from people with peanut allergy. Will this translate to a potential treatment for peanut allergy? We will have to wait and see.

For now, the more we learn about the action of allergens, and the more we understand their effects on our body, the more we can develop new ways to stop them. And eventually, we might outsmart these clever nuts for good.

Link:
Tough nuts: why peanuts trigger such powerful allergic reactions - The Conversation AU

DetailsCategory: VaccinesPublished on Monday, 16 December 2019 19:29Hits: 279

First allogeneic, off-the-shelf cell therapy approach that enhances T-cell activation through localized OX40-mediated co-stimulation of dormant immune signals

DURHAM, NC, USA I December 16, 2019 IHeat Biologics, Inc. (NASDAQ:HTBX), a clinical-stage biopharmaceutical company specialized in the development of therapeutics designed to activate patients' immune systems against cancer, today announced that the Company has dosed the first patient in the first Phase 1 clinical trial of HS-130, in combination with HS-110, for patients with advanced solid tumors refractory to standard of care.

HS-130 is Heat's allogeneic cell line engineered to locally secrete the extracellular domain of OX40 ligand fusion protein (OX40L-Fc), a key costimulator of T cells, designed to augment antigen-specific CD8+ T cell response. HS-130 was manufactured by utilizing the Company's proprietary process to reprogram a live, genetically modified cancer cell line. In multiple preclinical models, these responses have demonstrated improved efficacy and safety using OX40L-Fc via cell-based delivery compared to systemic delivery of an OX40 agonist antibody in combination with HS-110.

The first-in-human study is expected to enroll up to 30 patients under the supervision of lead investigator Dr. Rachel Sanborn, Director of the Phase 1 Clinical Trials Program at the Earle A. Chiles Research Institute, a division of Providence Cancer Institute in Portland, Oregon. In this study, patients will receive escalating doses of HS-130 in combination with HS-110. The objectives of the study are to evaluate patient safety and to determine the optimal dose for a subsequent Phase 2 trial.

Jeff Wolf, Heat's CEO, commented, "We are pleased to announce the initiation of this combination study, which marks a key milestone for Heat as we advance our latest asset into clinical development. We look forward to sharing clinical proof of concept data to enable the development of a new generation of allogeneic therapy drug candidates in 2020."

About HS-110

HS-110 is designed by engineering gp96-Fc to deliver more than 70 cancer testis antigens to stimulate the patients' immune system and activate a robust cytotoxic T cell response. HS-110 has completed enrollment in a Phase 2 clinical trial for advanced non-small cell lung cancer, in combination with Bristol-Myers Squibb's nivolumab (Opdivo) or with Merck's pembrolizumab (Keytruda) (NCT 02439450).

About HS-130

HS-130 is designed with the same parent cell line as HS-110 but is engineered to secrete OX40L-Fc fusion protein, a potent inducer of antigen-specific CD8+ T cell proliferation. The first-in-human study aims to evaluate the safety and dose-response of HS-130 in combination with HS-110 in patients with advanced solid tumors (NCT04116710).

About Heat Biologics, Inc.

Heat Biologics is a clinical-stage biopharmaceutical company developing novel therapeutics designed to activate a patient's immune system against cancer using CD8+ "Killer" T-cells. Pelican Therapeutics, Inc., a subsidiary of Heat, is focused on the development of co-stimulatory monoclonal antibody and fusion protein-based therapies designed to activate the immune system. For more information, please visit http://www.heatbio.com.

Reference

Fromm G, de Silva S, Giffin L, Xu X, Rose J, Schreiber TH. Gp96-Ig/Costimulator (OX40L, ICOSL, or 4-1BBL) Combination Vaccine Improves T-cell Priming and Enhances Immunity, Memory, and Tumor Elimination. Cancer Immunol Res. 2016 Sep 2;4(9):766-78.

SOURCE: Heat Biologics

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Heat Biologics Announces First Patient Dosed in the First Phase 1 Trial of HS-130 | Vaccines | News Channels - PipelineReview.com

Feng Li,1 Yan Chen,1,2 Shubo Liu,1 Xue Pan,1 Yulan Liu,1 Huiting Zhao,1 Xiujing Yin,1 Chunlin Yu,1 Wei Kong,1,2 Yong Zhang1,2

1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Peoples Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, Peoples Republic of China

Correspondence: Yong ZhangSchool of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, Peoples Republic of ChinaTel +86431 85167751Fax +86431 85167674Email zhangyongking1@gmail.com

Background: Zein-based carriers are a promising delivery system for biomedical applications. However, few studies involve systematic investigation on their in vivo biocompatibility and immunogenicity.Purpose: The objective of this study was to identify the immunogenicity, type of immune response, biocompatibility and systemic recall immune response of zein nanoparticles administrated via different routes in mice.Animals and methods: Female Balb/c mice were selected as the animal model in this paper. The effect of particle size, dose and inoculation routes on immunogenicity were systematically explored. The mice were challenged at week 50 via intramuscular and subcutaneous routes to investigate the systemic recall immune responses of zein nanoparticles. Hematoxylin and eosin staining was performed to investigate the biocompatibility of zein nanoparticles at injection sites.Results: The administration of zein particles by parenteral routes led to a long-term systemic immune response. Particle size did not affect zein-specific IgG antibody titers. IgG antibody titers and inflammatory cell infiltration at the injection sites resulting from intramuscular zein particle injection were significantly higher than those from subcutaneous injection of the same dose. For intramuscular inoculation, dose-dependent IgG antibody titers were observed after the third inoculation, while no significant difference was found via the subcutaneous route. For both routes, IgG titer showed a time-dependent decrease at all dose levels from week 5 onward, and finally plateaued at week 28. The IgG subtype assay showed a predominant Th2-type immune response for both administration routes. Challenge with zein nanoparticles at week 50 led to a significant increase in specific IgG titer at all dose levels, indicating systemic recall immune responses. Interestingly, IgG antibody levels in the subcutaneous groups showed a delayed decrease compared to those of the intramuscular injection groups at all dose levels.Conclusion: This study indicated that immunogenicity may be one of the key challenges of using zein nanoparticles as carriers via parenteral administration. Further investigation is needed to illustrate zein immunogenicity in other forms, and the possible effect of systemic recall immune response on in vivo pharmacokinetic characteristics.

Keywords: zein, protein carrier, drug delivery, immune response, intramuscular injection, subcutaneous injection, parenteral administration

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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The Effect of Size, Dose, and Administration Route on Zein Nanoparticl | IJN - Dove Medical Press