A woman with a genetic mutation thought to inevitably cause Alzheimers disease in peoples 50s escaped that fate, living into her 70s before she developed mild dementia and researchers think they know why.

In addition to the Alzheimers mutation, they reported on Monday, she has a rare form of a gene best known for producing molecules that help carry cholesterol through the bloodstream. Somehow, the second gene prevented the devastating consequences of the first, a finding that might one day open up new approaches to treating or preventing Alzheimers.

This is an excellent and thought-provoking study, said Dr. Michael Greicius of Stanford University School of Medicine, an expert in Alzheimers genetics who was not involved in the research. He emphasized, however, that because the patients combination of genes is exceedingly uncommon and possibly unique, the study published in Nature Medicine is hypothesis-generating but far from definitive.

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He and five other Alzheimers researchers cautioned that this is a single case report, not a large study, and the rarity of the womans genetics may well make it impossible to prove that the supposedly protective gene really did keep her from developing early-onset Alzheimers.

The woman (unnamed, to protect her privacy) belongs to a large extended Colombian family. Descended from a Basque couple who migrated to Colombia 300 years ago, roughly 1,200 of its 6,000 living members carry a mutation in a gene called PSEN1, discovered in 1987. The mutation (known as E280A) causes the brain to overproduce the protein fragment beta-amyloid, which forms sticky plaques between neurons and is a diagnostic hallmark (though not necessarily the cause) of Alzheimers.

Because the Colombian family is the largest single group with mutations that cause early-onset Alzheimers half of those with the gene develop mild cognitive impairment by age 44 and dementia by 49 they have been a key part of studies of the disease.

Through one such study, the woman came to the attention of neuropsychologist Yakeel Quiroz of Massachusetts General Hospital. The womans memory and thinking had been basically fine well into her 50s and 60s, her family said. Although brain imaging revealed extremely high levels of amyloid as is expected with PSEN1 only in her 70s did she develop mild cognitive impairment, three decades after relatives who also have the amyloid-superproducing PSEN1 mutation.

In fact, she has more amyloid plaques than relatives whose cognition began crashing in their 40s. She also has relatively low brain levels of tau, also a protein fragment but one that accumulates inside (and kills) neurons. She also has little neurodegeneration.

To figure out how the woman avoided early-onset Alzheimers, Quiroz and her colleagues sequenced her genome. One of her genes, APOE3, was extremely unusual: Both copies (one from her mother and one from her father) carried the rare Christchurch mutation, named for the New Zealand city where it was discovered in 1987. Despite that history, it is found almost exclusively in Latinos; Stanfords Grecius estimates that only about 1 in 100 million people have two copies.

Like every other human, the woman has thousands of other unusual genetic variants. But Quiroz zeroed in on the Christchurch mutation based on an algorithm that ranks variants for their role in particular diseases. Different forms of APOE have long been associated with Alzheimers: APOE4 raises the risk of developing the disease, APOE2 lowers the risk, and APOE3 is neutral (there is no APOE1). We felt confident the Christchurch variant of APOE3 was of interest, Quiroz said.

To test that hunch, she and her team studied how the Christchurch form of the APOE3 molecule interacts with other molecules that play a role in Alzheimers. In lab dishes, the Christchurch form didnt bind as well as ordinary APOE3 to sugar molecules (called heparan sulphate proteoglycans). Those sugars, previous studies showed, are critical enablers of tau, the neuron-killing Alzheimers-related molecule: Bound to APOE, the sugars allow tau to spread from one neuron to another, jumping around the brain in a dance as lethal as glowing embers in a wildfire.

The Christchurch mutation, Quiroz and her team concluded, dampens tau formation and neuronal death even when the brain is awash in amyloid.

If theyre right, it might be possible to prevent or treat Alzheimers through a route very different from removing brain amyloid, as most experimental drugs have (in virtually every case, without success). Instead, antibodies or other molecules that keep APOE from binding to the tau-spreading sugars could reproduce [the] potentially protective effect of the Christchurch mutation, including in people with ordinary genes, Quiroz and her colleagues wrote. That could have a profound impact on the treatment and prevention of Alzheimers disease.

Other scientists werent so sure. The main doubt: This patient, like everyone, has tens of thousands of other rare variants, any one of which might be why she did not develop early-onset Alzheimers as her PSEN1 mutation should have caused.

There are thousands of variants in our genome, said Nikolaos Robakis of the Icahn School of Medicine at Mount Sinai, who discovered one of the first mutations for early-onset Alzheimers. So, from the get-go, its unlikely that this is the one that let the woman escape what would have otherwise been her genetic fate.

One reason for doubt: Having one copy of the Christchurch variant (as seven of 117 members of the patients extended family do) rather than two (as she does) has apparently no benefit, Stanfords Greicius pointed out. All of the seven developed early-onset Alzheimers.

It would have been most convincing to show that while two copies of the Christchurch variant move the age of onset from early 40s to early 70s, one copy had a middling effect, moving the age to the early 50s, he said. But there was no dose effect. That, agreed Robakis, is evidence against the claim that this rare form of APOE3 acts as an anti-Alzheimers talisman.

But even skeptics agreed on one thing: The role of APOE in Alzheimers is vastly understudied. Remedying that could be the Colombian womans most valuable contribution to Alzheimers research.

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She was destined to get early Alzheimer's, but didn't. Did a rare mutation protect her - STAT

Could one woman's rare genetic mutation one day have a global impact on dementia risk?

It's possible, say investigators who report on a potentially groundbreaking case of a woman whose genetic mutation staved off dementia for decades, even though her brain hadalreadybeen damaged by Alzheimer's disease.

While most Alzheimer's cases are not driven by genetic predisposition, one woman in Colombia is among about 1,200 in her country who do face a genetically higher risk for early-onset Alzheimer's.

Why? They all carry the E280A mutation of a gene called Presenilin 1 (PSEN1), which is known to increase the chances for Alzheimer's at a far younger age than usual.

"We identified an individual that was predisposed to develop Alzheimer's in her 40s," noted study author Dr. Joseph Arboleda-Velasquez. He's an assistant professor of ophthalmology with the Schepens Eye Research Institute of Mass Eye and Ear at Harvard Medical School, in Boston.

But, strangely, the woman "remained unimpaired until her 70s," Arboleda-Velasquez added.

The twist: the woman had, in fact, developed clear telltale signs of Alzheimer's in her brain. She just hadn't developed dementia.

For example, while she had fewer neural "tangles" in her brain than is typical for Alzheimer's patients, by the time she hit her 40s she did have the same unusually high level of brain amyloid-beta deposits as her E280A peers. Such deposits are a key signature of Alzheimer's.

So why didn't she develop middle-aged dementia like her peers?

To unravel the mystery, Arboleda-Velasquez and his colleagues ran an in-depth genetic analysis on the woman. And what they found is that she had not just one mutation, but two.

In addition to the E280A mutation, she also carried the so-called "Christchurch" mutation in the APOE3 gene.

But there's more. Not only did she carry the Christchurch mutation, but she hadtwoof them. Some of her E280A peers (about 6%) also carried a single copy of Christchurch. But she was the only one who carried two, the investigators found.

"It is ultra-rare, with an approximate prevalence of less than one in every 200,000 individuals," Arboleda-Velasquez said.

And having one such rare mutation did not appear to be enough. No protection against dementia was linked to only one Christchurch mutation. But as this woman's case suggests, having two such mutations did seem to throw up a shield against Alzheimer's, preserving her ability to remember things and think clearly for a few decades, long after her E280A peers had started experiencing cognitive decline.

"This is the first time a specific patient who carries the [double] mutation has been linked to such a protective benefit," Arboleda-Velasquez noted.

How does it work? It seems that "the mutation puts a block on the cascade of events linking amyloid accumulation to neural [brain cell] death," he explained.

The team did acknowledge that more research will be needed to definitively confirm the Christchurch mutation's impact, and to further explore how this mutation/dementia delay connection truly works.

But, in theory, the incredibly rare experience of this one woman in Colombia could ultimately have profound ramifications for Alzheimer's patients around the world, if "new drugs that mimic the effect of [the] mutation" could be developed, said Arboleda-Velasquez. Rather than stopping Alzheimer's from developing, such drugs would prevent Alzheimer's from causing dementia.

The study was published Nov. 4 in the journalNature Medicine, and was partly funded by the U.S. National Institutes of Health and the Alzheimer's Association.

Heather Snyder, vice president of medical and scientific relations at the Alzheimer's Association, characterized the findings as "an important discovery."

The insights gleaned from a look at this particular patient's experience are "full of possibilities for increasing our understanding of Alzheimer's disease and all dementia, and advancing potential avenues for treatment," Snyder suggested.

"Understanding what is happening in the brains of people when there appears to be a delay or stopping of the disease progression because of this gene form or otherwise gives rise to many possibilities for investigating new treatment and risk-reduction opportunities," she added.

At the same time, Snyder cautioned that "more research is needed to understand more thoroughly how genetics impacts Alzheimer's/dementia risk, and to expand and confirm these findings in a larger number of people."

Link:
Alzheimer's disease: Rare genetic mutation might hold clues to preventing or treating dementia - CBS News

Ilana Yurkiewicz, a physician and medical journalist at Stanford University, explains why CAR-T is only used in patients with certain cancers and tries to answer why they havent yet been shown to work against solid tumors in an UnDark article. Public health news is on breast cancer tests, fecal matter transplants, Zantac recalls, white male life expectancy, skin rashes, growing up with HIV, a retracted HIV study, live-streaming a mammogram, and how to get a good night's sleep, as well.

The Washington Post:Science Author Digs Into The Story About A Revolutionary Cancer Treatment Used In ImmunotherapyIn 2017, CAR-T therapy made waves as the first gene therapy to be approved by the Food and Drug Administration. In a fascinating article for Undark, Ilana Yurkiewicz, a physician at Stanford University, plunges into the fraught history and future of a cancer treatment thats as radical as it is risky. Unlike chemotherapy or radiation, which attack cancer directly, CAR-T engineers patients immune cells so they can do it themselves. (Blakemore, 11/2)

Bloomberg:Blood Test To Detect Breast Cancer Could Be Five Years AwayA blood test that may be able to detect breast cancer up to five years before symptoms develop could be available by 2025 if development is fully funded, U.K. researchers said. Doctors at the Centre of Excellence for Autoimmunity in Cancer at the University of Nottingham compared blood samples from 90 patients being treated for breast cancer with the same number from a control group without the disease to measure the bodys immune response to substances produced by tumor cells. Theyre now testing samples from 800 patients for nine markers and they expect the accuracy of the test to improve. (Marley, 11/3)

Stat:FDA To Consider New Evidence, Risks Behind Fecal Matter TransplantsOn Monday, the Food and Drug Administration will host its first formal discussion about fecal microbiome transplants in years less than a week after a paper in the New England Journal of Medicine disclosed new details about the first death ever conclusively linked to the procedure, often abbreviated to FMT. The Monday meeting, which will be happening at the FDAs headquarters in White Oak, Md., will cover the safety and effectiveness of FMT as a treatment for repeated (and potentially fatal infections) of Clostridium difficile bacteria. (Sheridan, 11/1)

Stat:FDA: Zantac Does Not Form A Carcinogen, But Some Pills Should Be RecalledAfter running simulated testing, the Food and Drug Administration says it has not found evidence that Zantac and similar heartburn medicines form a possible carcinogen in patient stomachs or small intestines. Nonetheless, the agency also indicated some of the medicines contain higher than acceptable levels of NDMA, and asked manufacturers to voluntarily withdraw those pills. The move marks the first time the FDA has suggested drug makers should recall their heartburn medicines, which are called ranitidines, after opening a probe several weeks ago. (Silverman, 11/1)

CBS News:Life Expectancy For American Men Drops For A Third YearLife expectancy for American men dropped for a third consecutive year, with the National Center for Health Statistics citing an increase in so-called "deaths of despair," such as the rise in drug overdose deaths.The average lifespan of men in the U.S. dipped to 76.1 years in 2017 (the latest data available), amounting to a four-month decline in life expectancy since 2014. The findings shed additional light on economic research into the sharp increase in recent years in deaths from overdoses and suicides among white men with less education. (Picchi, 10/31)

NPR:Rashes Can Look Very Different On Different Shades Of SkinWhen Ellen Buchanan Weiss' son was about a year old, he broke out in a rash little bumps that appeared to be hives. So Buchanan Weiss did what a lot of new parents do: She turned to the Internet to find images that matched the rash she was seeing on her little boy. "I'm trying to figure out would I be paranoid if I went to the doctor at this point? Is that a reasonable thing to do? So I started googling it," says Buchanan Weiss, who lives with her family in Raleigh, N.C. (Prichep, 11/4)

The New York Times:Armed With A New Laptop, He Is On A Path To A DegreeWhen he was growing up, Warren Williams wanted nothing more than to play baseball and watch Scooby-Doo. I just wanted to be normal, like other kids, he said. But his health often took the joy out of his childhood. Mr. Williams, 26, was born with H.I.V. One of his earliest memories is from when he was 4: A mass had developed in his chest and he was rushed to a hospital to have open-heart surgery. The doctors gave him a stuffed Barney the dinosaur to keep by his side on the operating table. (Aridi, 11/3)

The Associated Press:Scientists Retract Study Suggesting Mutation Shortens LifeScientists have retracted a study that appeared to show people may live shortened lives if they carry a DNA mutation that reduces their chance of HIV infection. The study focused on people who carry a specific mutation in both copies of a gene called CCR5. It was published in June in the journal Nature Medicine and covered by news outlets including The Associated Press. (11/1)

The Washington Post:Ali Meyer Records Breast Cancer Diagnosis Live On Facebook For KFOR NewsAli Meyer live-streamed her first mammogram with other women in mind. The veteran journalist was wary of making herself the center of the story, she remembers, but she wanted to remind people to schedule their own appointments so they could catch breast cancer early. Then a nurse came in to say the radiologist would prefer to see Meyer with the camera off. In private, the doctor told Meyer she would need more imaging. At 40 years old, she realized, she might have cancer. (Knowles, 11/2)

NPR:How To Fall Asleep: These Daytime Habits Will HelpIf turning back the clock an hour for the end of daylight saving time leaves you feeling jangly, imagine the toll that chronic sleep loss can take on your health. The evidence has piled up. We all need good sleep. And our bodies crave regular routine. Without it, we set up ourselves for increased risk of anxiety, depression, weight gain, even dementia. (Aubrey, 11/3)

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Physician Goes Behind The Scenes To Write Compelling Story About Treating Patients With New Cancer Gene Therapy - Kaiser Health News

BARCELONA Researchers have obtained the first signs of clinical benefit in an early-stage gene therapy trial for Tay-Sachs disease, according to a presentation at the European Society of Gene & Cell Therapy (ESGCT) annual conference last week.

Terence R. Flotte, MD, executive deputy chancellor, provost, and dean of the University of Massachusetts (UMass) School of Medicine, presented the results in Barcelona. Flotte is also the editor-in-chief of Human Gene Therapy (a sister journal of GEN).

Buckle your seatbelts, commented Fyodor Urnov, PhD, a gene therapy expert at the Innovative Genomics Institute, UC Berkeley, on Twitter. A gene therapy early-stage success for Tay-Sachs!!!

Urnov said: Flotte has long been an inspiration and a leader for the field, and this is just MAGNIFICENT. Tay-Sachs is devastatingbut perhaps for not much longer?

Tay-Sachs is an incurable recessively inherited pediatric genetic disease, a member of a group of lysosomal storage diseases, which is particularly common in individuals of Ashkenazi Jewish descent. Patients have a median life expectancy of approximately three to four years.

Flotte presented preliminary data on two infants in the Phase I trial, which is designed to ascertain safety rather than efficacy. But Flotte said there are early signs that the therapy, which in 2018 was licensed to Axovant Gene Therapies, has the potential to modify the rate of disease progression.

Flotte said that the adeno-associated virus (AAV) gene therapyAXO-AAV-GM2had been successfully administered in both children and has been well tolerated so far, with no serious adverse events or clinical abnormalities related to the therapy. The route of therapy is significant: it involves bilateral intrathalamic and intrathecal injection of the virus in an effort to deliver widespread distribution of the replacement enzymehexosaminidase A (HexA) throughout the brain and central nervous system.

This innovative delivery could overcome one of the primary challenges for developing treatments for Tay-Sachs, Sandhoff, and many other severe pediatric genetic disorders, providing much needed hope for these families, Flotte said.

Flotte said there had been a very modest increase in HexA bioactivity in both patients (less than two percent). More encouragingly, the second patient treated showed signs of increased myelination and a plateau in disease development.

The data presented by Flotte marked the first reported evidence for potential disease modification in Tay-Sachs disease, and suggest an opportunity for gene replacement therapy to improve outcomes for children with this devastating condition, said Gavin Corcoran, MD, Axovants chief research and development officer, in a statement.

Myelination is an important component of healthy brain development in infants and is often abnormal in children with Tay-Sachs disease. We were encouraged to see MRI evidence of preserved brain architecture and improved myelination in the early symptomatic child treated at 10 months of age, Corcoran said.

Flotte presented the preliminary trial findings on behalf of his UMass colleagues including Miguel Sena-Esteves, PhD, associate professor of neurology; Heather Gray-Edwards, PhD, DVM, assistant professor of radiology; and Douglas Martin, PhD, professor of anatomy, physiology, and pharmacology in the College of Veterinary Medicine at Auburn University.

A Phase II trial is being planned.

Flottes report was one of several highlights delivered at the ESGCT annual congress, which attracted a record attendance of more than 2,000 scientists last week. Flotte was one of many leading plenary speakers, including Carl June, MD (University of Pennsylvania) and Michel Sadelain, MD (Memorial Sloan Kettering) on CAR-T therapy; David Williams, MD (Boston Childrens Hospital), Matthew Porteus, MD (Stanford University), and Donald Kohn, MD (UCLA) on gene therapy for sickle-cell disease and beta-thalassemia; Fulvio Mulvilio, MD (Audentes Therapeutics) on X-linked myotubular myopathy; and James Wilson, MD (University of Pennsylvania) on safety of gene-editing nucleases.

The conference also marked the third public presentation of prime editing, the novel genome editing technology developed by David Liu, PhD (Broad Institute/HHMI) and colleagues, which was published last week in Nature. The method offers the possibility of engineering any base substitution by using an RNA intermediate.

Despite recent protests in Barcelona, the conference proceeded without incident. The 2020 ESGCT congress will be held in Edinburgh, Scotland, on October 20-23, in collaboration with the British Society for Gene and Cell Therapy.

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Promising Results Reported in Tay-Sachs Gene Therapy Trial - Genetic Engineering & Biotechnology News

Nov. 2, 2019 13:30 UTC

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Veracyte, Inc. (Nasdaq: VCYT) today announced new data that advance understanding of the frequency, positive predictive value and co-occurrence of genomic alterations that are targeted by newly available and investigational precision medicine therapies for thyroid cancer. The findings were enabled by Afirma Xpression Atlas analyses, which uses RNA sequencing, of Veracytes extensive biorepository of thyroid nodule fine needle aspiration (FNA) samples from patients undergoing evaluation for thyroid cancer. The data were presented this week during the 89th Annual Meeting of the American Thyroid Association (ATA).

In one study, researchers assessed the frequency of ALK, BRAF, NTRK and RET fusions in nearly 48,000 consecutive patients whose thyroid nodule FNA samples were deemed indeterminate, suspicious for malignancy or malignant (Bethesda III/IV, V and VI categories, respectively) by cytopathology. The researchers found that 425 (0.89 percent) of the FNA samples harbored one of the alterations, with NTRK fusions the most common at 0.38 percent, followed by RET (0.32 percent), BRAF (0.13 percent) and ALK (0.06 percent). Additionally, RNA whole transcriptome sequencing demonstrated differences in the prevalence of these four fusions across Bethesda categories, with Bethesda V being the highest.

NTRK fusion inhibitors have received pan-cancer FDA approval and clinical trials have included selective inhibitors of ALK, BRAF, NTRK and RET, which makes their detection in patients with thyroid cancer of interest to physicians, said Mimi I. Hu, M.D., professor at The University of Texas MD Anderson Cancer Center, who presented the findings in a poster. As our understanding of the role of genomics in thyroid cancer advances, this information offers the potential to optimize initial treatment, predict response to treatment and prioritize selective targeted therapy should systemic treatment be needed.

In another study, researchers evaluated the positive predictive value of the NTRK, RET, BRAF and ALK fusions in 58 patients with indeterminate thyroid nodules (Bethesda III/IV categories) from Veracytes biorepository for whom surgical pathology diagnoses were available. They found that NTRK and RET fusions were associated with malignancy in 28 of 30 nodules, while risk of malignancy was lower among nodules with ALK (67 percent) or BRAF (75 percent). In a third study, researchers found that when using RNA sequencing data on a large sample of nearly 48,000 thyroid nodule FNA samples (Bethesda categories III-VI), they identified 263 co-occurrences of gene fusions and variants that were previously considered mutually exclusive.

The findings from these three studies underscore the power of our extensive biorepository of thyroid nodule FNA samples and our optimized RNA sequencing platform to advance understanding of the genomic underpinnings of thyroid cancer and to better capture the biology of thyroid lesions, said Richard T. Kloos, M.D., senior medical director, endocrinology, at Veracyte. As precision medicine therapies that target specific gene alterations emerge, understanding individual patients genomic profiles becomes increasingly important to physicians. Our Afirma Xpression Atlas provides this information at the same time as initial diagnosis with the Afirma Genomic Sequencing Classifier, or GSC, to help inform treatment decisions.

Also during the ATA meeting, Veracyte unveiled its new Afirma patient report, which in addition to identifying patients with benign or suspicious-for-cancer nodules among those deemed indeterminate by cytopathology, based on Afirma GSC results, now provides individualized and actionable variant and fusion information on each patient. This information includes: risk of malignancy, associated neoplasm type, relative risk of lymph node metastasis and extrathyroidal extension; availability of FDA-approved therapy; and genetic counseling and germline testing considerations. This information is also provided for patients with cytopathology results that are suspicious for malignancy or malignant (Bethesda V and VI).

About Afirma

The Afirma Genomic Sequencing Classifier (GSC) and Xpression Atlas provide physicians with a comprehensive solution for a complex landscape in thyroid nodule diagnosis. The Afirma GSC was developed with RNA whole-transcriptome sequencing and machine learning and helps identify patients with benign thyroid nodules among those with indeterminate cytopathology results in order to help patients avoid unnecessary diagnostic thyroid surgery. The Afirma Xpression Atlas provides physicians with genomic alteration content from the same fine needle aspiration samples that are used in Afirma GSC testing and may help physicians decide with greater confidence on the surgical or therapeutic pathway for their patients. The Afirma Xpression Atlas includes 761 DNA variants and 130 RNA fusion partners in over 500 genes that are associated with thyroid cancer.

About Veracyte

Veracyte (Nasdaq: VCYT) is a leading genomic diagnostics company that improves patient care by providing answers to clinical questions that inform diagnosis and treatment decisions without the need for costly, risky surgeries that are often unnecessary. The company's products uniquely combine RNA whole-transcriptome sequencing and machine learning to deliver results that give patients and physicians a clear path forward. Since its founding in 2008, Veracyte has commercialized seven genomic tests and is transforming the diagnosis of thyroid cancer, lung cancer and idiopathic pulmonary fibrosis. Veracyte is based in South San Francisco, California. For more information, please visit http://www.veracyte.com and follow the company on Twitter (@veracyte).

Cautionary Note Regarding Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan," "expect," "believe," "should," "may," "will" and similar references to future periods. Examples of forward-looking statements include, among others, the ability of Veracytes Afirma Xpression Atlas to analyze FNA samples to help diagnose thyroid cancer, the expected impacts of Veracytes collaboration with Johnson & Johnson in developing interventions for lung cancer, on Veracytes financial and operating results, on the timing of the commercialization of the Percepta classifier, and on the size of Veracytes addressable market. Forward-looking statements are neither historical facts nor assurances of future performance, but are based only on our current beliefs, expectations and assumptions. These statements involve risks and uncertainties, which could cause actual results to differ materially from our predictions, and include, but are not limited to: our ability to achieve milestones under the collaboration agreement with Johnson & Johnson; our ability to achieve and maintain Medicare coverage for our tests; the benefits of our tests and the applicability of clinical results to actual outcomes; the laws and regulations applicable to our business, including potential regulation by the Food and Drug Administration or other regulatory bodies; our ability to successfully achieve and maintain adoption of and reimbursement for our products; the amount by which use of our products are able to reduce invasive procedures and misdiagnosis, and reduce healthcare costs; the occurrence and outcomes of clinical studies; and other risks set forth in our filings with the Securities and Exchange Commission, including the risks set forth in our quarterly report on Form 10-Q for the quarter ended September 30, 2019. These forward-looking statements speak only as of the date hereof and Veracyte specifically disclaims any obligation to update these forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law.

Veracyte, Afirma, Percepta, Envisia and the Veracyte logo are trademarks of Veracyte, Inc.

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Veracyte Announces New Data That Advance Understanding of Genomic Alterations Targeted by Precision Medicine Therapies for Thyroid Cancer - BioSpace

Type 2 diabetes affects almost 400 million people across the world. Diabetes is caused by a combination of lifestyle as well as genetic factors which together result in high blood sugar levelsOne such genetic factor that can influence blood sugar levels is a variation in a gene called SLC30A8, which encodes a protein which carries zinc.

This protein is important, because zinc is essential for ensuring that insulin, (the only hormone that can reduce blood sugar levels) has the right shape in the beta-cells of the pancreas.

Researchers have known for almost ten years that changes in this gene can reduce the risk of getting type 2 diabetes, but not how this happened. They now recruited new members from families with a rare mutation in the SLC30A8 gene to study how they responded to sugar in a meal.

Departmental chief doctor Tiinamaija Tuomi from the Helsinki University Hospital, who co-led the study, said: A definite strength of our study is we could study families. We could compare people with the mutation with their relatives who do not have the mutation, but who have similar genetic background and life-style.

This way, we could make sure that the effects we were seeing were definitely because of this gene, and not because of another genetic or life-style factor.

The results showed that people with the mutation have higher insulin and lower blood sugar levels, reducing their risk for diabetes.

An international collaboration of 50 researchers also studied pancreatic cells with and without the mutation in the lab and carried out experiments in mice and human cellular material to understand exactly what was happening when the function of the SLC30A8 gene changed.

Professor Anna Gloyn, who co-led the study, from the Wellcome Centre for Human Genetics, University of Oxford, said: The work is a collaborative effort bringing pharma and academia together and researchers from multiple European Countries. It is a tour de force, since we were able to measure the impact of the mutation in many different systems, including human beta-cells.

Dr Benoit Hastoy, co-first author from the Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford said: We found that this mutation had collateral consequences on key functions of pancreatic beta cells and during their development. Importantly, this study exposes the extraordinary molecular complexity behind a specific gene variation conferring risk or protection from type 2 diabetes.

Taken together, the human and model system data show enhanced glucose-stimulated insulin secretion combined with enhanced conversion of the prehormone proinsulin to insulin as the most likely explanation for protection against type 2 diabetes, said Om Prakash Dwidedi, the co- first author of the study from the Institute for Molecular Medicine Finland (FIMM), University of Helsinki.

Better understanding of the genetic and pathological mechanism behind diabetes can open up new ways of preventing or treating type 2 diabetes.

Professor Leif Groop from the University of Helsinki and the Lund University who directed the study, added: Our results position this zinc transporter as an appealing and safe target for antidiabetic therapies. If a drug can be developed that mimics the protective effect of this mutation, beta-cell function could be preserved and the insulin secretion capacity in diabetic patients maintained.

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New study decodes gene function that protects against type 2 diabetes - Health Europa

Following the successful fundraising for Zente and Levente, two Hungarian toddlers suffering from SMA (spinal muscular atrophy) for their 700 million HUF treatment, themost expensive medicine in the world, Hungary has come together again for a third boy suffering from SMA Noel, who lives in rkrtvlyes in Bihar county, Romania.

Noels mother reported on a Facebook page created for the baby, who is only a few months old, is suffering from the same illness as the two other boys who recently received the support of a whole country, which made it possible for them to receive treatment. The family has created a foundation, but people can donate to multiple bank accounts as well.

Fundraiser Set up for Another Toddler to Receive Worlds Most Expensive Medicine

The mother emphasized that she would like to point out that I not only ask Hungarian people and those living in Hungary to help. We created the site in Hungarian because it is our mother tongue and because there are many helpful Hungarian people living here in Romania as well. Of course, translations are being made.

They have already taken the necessary steps and are waiting for an approval for Noel to receive another medicine, Spinraza, which will help him to develop, and for his condition to not further deteriorate. The Spinraza injection is financed completely by the National Health Insurance Fund (NEAK). The vaccine was patented just last year. This treatment is not cheap either, as an injection costs 23 million HUF, but the cost is entirely borne by NEAK. However, this medicine is needed by patients for the rest of their lives.

Fundraising for Toddlers Expensive Treatment Moves Hungary

This is why they have also set up fundraising to receive a medicine which is only needed once to improve the babys condition. However, this expensive medicine, called Zolgensma, is currently the most expensive medicine in the world and it has only been on the market since May.

SMA-1 is an extremely rare genetic disorder which affects only one in eight to ten thousand people. Because of a defective gene, their body does not produce the protein that protects muscle cells, so their muscles slowly deteriorate. Symptoms of SMA-1 usually occur during the first months of the patients life. In most cases, due to respiratory paralysis, children do not reach age two. There are approximately 120 SMA patients officially registered in Hungary (this applies to all types of SMA, not just SMA-1) but due to the outdated registration system, professionals say that the actual number is around 300.

The essence of the treatment is that the patients are given a virus by gene therapy that infects and replaces the gene pool of defective or missing motor neurons, thus preventing muscular atrophy.In Hungary, another treatment may have given hope to SMA patients as of last year, but for the time being, it is only funded on a case-by-case basis, exclusively for children.

featured photo: Noel and his family. (photo:Kicsi Noel SMA 1 Facebook)

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Fundraising Started for Another Baby with SMA to Receive World's Most Expensive Medicine - Hungary Today

Alignment With FDA on GMP Commercial Manufacturing Process for KB103 (Bercolagene telserpavec, B-VEC)KB105 Granted Fast Track Designation by the FDAPlatform Patent for Delivering any Effector to the Skin Granted by USPTO

PITTSBURGH, Nov. 04, 2019 (GLOBE NEWSWIRE) -- Krystal Biotech Inc., (Krystal) (KRYS), a gene therapy company developing medicines to treat dermatological diseases, announced financial results for third quarter 2019, recent corporate highlights and upcoming milestones.

"Following our CMC meeting, we believe we have a scalable GMP commercial process in place to fulfill future patient demand and anticipate a modest impact to our previously disclosed B-VEC timeline, said Krish S. Krishnan, chairman and chief executive officer of Krystal Biotech. We plan on announcing our agreement with the FDA on trial design and endpoints prior to initiating the B-VEC pivotal trial.

Corporate Highlights

CMC alignment and End of Phase 2 meeting

Positive results from Phase 1/2 trial of B-VEC

KB105

Patents

Pipeline

Financial results for the quarter endedSeptember 30, 2019

For additional information on the Companys financial results for the quarter ended September 30, 2018, refer to form 10-Q filed as with the SEC.

About KB103KB103 is Krystals lead product candidate, currently in clinical development, seeks to use gene therapy to treat dystrophic epidermolysis bullosa, or DEB, an incurable skin blistering condition caused by a lack of collagen in the skin.KB103 is a replication-defective, non-integrating viral vector that has been engineered using the HSV-1 virus employing Krystals STAR-D platform to deliver functional human COL7A1 genes directly to the patients dividing and non-dividing skin cells.Krystals vector can penetrate skin cells more efficiently than other viral vectors.Its high payload capacity allows it to accommodate large or multiple genes and its low immunogenicity makes it a suitable choice for direct and repeat delivery to the skin.

About Dystrophic Epidermolysis Bullosa, or DEBDystrophic epidermolysis bullosa, or DEB, is an incurable, often fatal skin blistering condition caused by a lack of collagen protein in the skin. It is caused by mutations in the gene coding for type VII collagen, or COL7, a major component of the anchoring fibrils, which anchor the epidermis to the underlying dermis, and provide structural adhesion in a normal individual. The lack of COL7 in DEB patients causes blisters to occur in the dermis as a result of separation from the epidermis.This makes the skin incredibly fragile, leading to blistering or skin loss at the slightest friction or knock. It is progressive and incredibly painful.

The most severe form of DEB is recessive DEB, or RDEB, which is caused by null mutations in the COL7A1 gene.DEB also occurs in the form of dominant DEB, or DDEB, which is considered to be a milder form of DEB.There are no known treatments which affect the outcome of either form of the disease, and the current standard of care for DEB patients is limited to palliative treatments.Krystalis developing KB-103 for the treatment of the broad DEB population, including both recessive and dominant forms of the disease.

About KB105KB105 is Krystals second product candidate, currently in clinical development, seeks to use gene therapy to treat patients with TGM-1 deficient ARCI. KB105 is a replication-defective, non-integrating viral vector that has been engineered employing Krystals STAR-D platform to deliver functional human TGM-1 gene directly to the patients dividing and non-dividing skin cells.

About Autosomal Recessive Congenital IchthyosisTransglutaminase 1 (TGM-1) is an essential epidermal enzyme that facilitates the formation of the epidermal barrier, which prevents dehydration, and protects the skin from unwanted toxins and surface microorganisms. The loss of TGM-1-activity results in the severe genetic skin disease autosomal recessive congenital ichthyosis (ARCI). Most patients with a TGM-1-deficiency exhibit life-long pronounced scaling with increased trans epidermal water loss (TEWL). The scales are plate-like, often of a dark color, and cover the whole-body surface area. Erythroderma is either absent or minimal. Such patients usually have ectropion and, at times, eclabium, hypoplasia of joint and nasal cartilage, scarring alopecia, especially at the edge of the scalp, and palmoplantar keratoderma. Additional complications include episodes of sepsis, fluid and electrolyte imbalances due to impaired skin barrier function, and failure to thrive, especially during neonatal period and infancy. Severe heat intolerance, and nail dystrophy are also frequently observed. TGM-1-deficient ARCI is associated with increased mortality in the neonatal period and has a dramatic impact on quality of life. No efficient treatment is available; current therapy only relieves some symptoms. There are approximately 23,000 cases of TGM1 deficient ARCI worldwide and about 400 new cases per year globally.

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About the STAR-D Gene Therapy PlatformKrystalhas developed a proprietary gene therapy platform, the Skin TARgeted Delivery platform, or STAR-D platform, that consists of an engineered HSV-1 viral vector and skin-optimized gene transfer technology, to develop off-the-shelf treatments for dermatological diseases. We believe that the STAR-D platform provides an optimal approach for treating dermatological conditions due to the nature of the vector. Certain inherent features of the HSV-1 virus, combined with the ability to strategically modify the virus in the form employed as a gene delivery backbone, provide the STAR-D platform with several advantages over other viral vector platforms for use in dermatological applications.

AboutKrystal BiotechKrystal Biotech, Inc.(KRYS) is a gene therapy company dedicated to developing and commercializing novel treatments for patients suffering from dermatological diseases. For more information, please visithttp://www.krystalbio.com.

Forward-Looking StatementsThis press release includes certain disclosures that contain forward-looking statements, including, without limitation, statements regarding development timelines for KB103, the ability of KB103 to be a transformative treatment option for DEB patients and the ability of our Ancoris manufacturing facility to supply KB103 for the forthcoming clinical trial . You can identify forward-looking statements because they contain words such as anticipate, believes and expects. Forward-looking statements are based on Krystals current expectations and assumptions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that may differ materially from those contemplated by the forward-looking statements, which are neither statements of historical fact nor guarantees nor assurances of future performance. Important factors that could cause actual results to differ materially from those in the forward-looking statements are set forth in Krystals filings with theSecurities and Exchange Commission, including its registration statement on Form S-3, and in its Forms 10-K and 10-Q, as modified or supplemented from time to time, under the caption Risk Factors.

CONTACTS:

Investors:Ashley R. RobinsonLifeSci Advisorsarr@lifesciadvisors.com

Media:Darren Opland, PhD LifeSci Public Relationsdarren@lifescipublicrelations.com

Source: Krystal Biotech, Inc.

Link:
Krystal Biotech Reports Third Quarter 2019 Financial and Operating Results - Yahoo Finance