Aniridia is a congenital disorder that causes severe eye problems, and also affects metabolism sometimes resulting in severe obesity. It is associated with mutation of a major developmental gene, called PAX6. People born with aniridia have no irises in their eyes, often are legally blind, and whatever eyesight they have continually worsens with age. The disease is uncommon, but disorders associated with genetic mutations can involve common eye problems, including cataracts and glaucoma.

To better understand and treat aniridia and other disorders involving the PAX6 gene, researchers and clinicians at the University of Virginia are combining clinical research, patient treatment and powerful basic science investigations.

They have organized for this weekend a major symposium focused on congenital eye disorders and the PAX6 gene, bringing together top researchers from the University and around the nation and Europe, along with patients living with aniridia and their families.

The organizers are Rob Grainger, W.L. Lyons Brown Professor of Biology, and Dr. Peter Netland, Vernah Scott Moyston Professor and Chair of Ophthalmology. Both are members of UVAs Brain Institute, and are research collaborators.

In his studies, Grainger uses frogs that are mutated to mimic aniridia and other eye disorders. Netland treats congenital eye disorders and conducts clinical research.

Here, the two colleagues explain for UVA Today readers their research and the goals of the 2019 John F. Anderson Symposium, Aniridia-PAX6 and Beyond

Q. Why did you organize this particular kind of symposium, connecting how eyes develop before birth and genetic diseases that can follow?

Grainger: Each of us works on different perspectives concerning eye formation. In my lab, we focus on how the eye is constructed during embryonic development; in Peter Netlands practice, on how to treat diseases that affect these processes.

These are complementary approaches two sides of the same coin. In one case we focus on the assembly of the eye, and in the other, what occurs when the eye is not constructed properly, leading to multiple serious consequences for the patient.

This interplay highlights the importance of looking at these two perspectives together, a collaboration in this case between the two of us (one in the School of Medicine and the other in the College of Arts & Sciences) each providing insights for the other.

Netland: The value of this kind of interaction has motivated us to bring together many of the worlds experts who pursue these two perspectives, including as well a third group: patients and their families who want to learn more about these diseases and treatments. There are few meetings held with this sort of three-way interaction in mind, and we anticipate that many fruitful insights and collaborations will emerge.

Q. Dr. Netland, why is aniridia an area of particular interest to you?

Netland: More than 20 years ago, I spent an extended period of time in the Middle East and India, where there are high rates of consanguinity and congenital eye disorders, which led to a book I produced about pediatric glaucomas, other scholarly contributions and development of my clinical skills. About 20 years ago, I cared for an infant with aniridia and the family of that patient. The potentially disabling issues for the patient, which involved all parts of the eye, and the compelling issues that the family were dealing with drew me toward this condition.

Another patient was very influential to me, because she was a patient advocate and mother of an affected child. I began to see increasingly larger numbers of patients with congenital eye disorders and aniridia, and I developed further clinical and academic interests in the topic.

Around 20 years ago, we started biannual meetings with the patient advocacy group Aniridia Foundation International, and developed connections with other patient support groups, which helped shape the direction of our efforts. With increasing contact with the patients and their families, I became deeply interested in trying to help these patients.

About 20 years ago, I cared for an infant with aniridia and the family of that patient. The potentially disabling issues for the patient, which involved all parts of the eye, and the compelling issues that the family were dealing with drew me toward this condition.

- Dr. Peter Netland

This is a disease that results from damage to the gene PAX6, already known to be perhaps the most fundamental gene involved in eye formation overall and consequently affecting the entire visual system. However, we knew much less about how to treat the many facets of this disorder; for example, cataract, glaucoma and corneal opacification (scarring), which are frequently acquired by patients. Some of these problems are common in the general population, and have broad significance. Many advances have been made in the past, but there is much more progress that is needed for the future.

Q. Why do you use frogs in your eye research, Professor Grainger?

Grainger: We have been examining eye development in frog embryos for over 20 years in my lab, initially because so much embryology, going back to the beginning of the 20th century, was done on these large, easy-to-obtain-and-raise embryos.

In the early days, we were learning how the different parts of the eye, notably the lens and retina, are formed by interactions between parts of the embryo to form a coordinated whole organ exactly the interactions that are disturbed when things go awry in aniridia patients.

Q. Six years ago the Grainger lab developed a gene-editing technique that allows you to mimic human lesions. How is this advancing eye research?

Grainger: While the utility of the frog system for understanding embryological processes is undisputed, during the decades that we have been doing research, the techniques allowing us to manipulate and understand gene function have blossomed, including genome projects and more recently gene editing the ability to inactivate genes of interest to learn how they function during normal development.

In 2013, we published our first paper using this new technology to inactivate genes critical for eye formation in frogs and to follow in precise detail how things go awry. This has allowed us to make important clarifications in how these genes contribute to development of the eye. Because the frog eye develops much as the human eye, these mutations help us look in detail in a way not feasible in human embryos; thereby allowing us to understand how these genetic errors lead to the problems that occur in human patients. Specifically, we have made mutations in frogs in the PAX6 gene that lead to frogs having aniridia, with features of the animals strikingly similar to those in human patients.

These are complementary approaches two sides of the same coin. In one case we focus on the assembly of the eye, and in the other, what occurs when the eye is not constructed properly, leading to multiple serious consequences for the patient.

- Robert Grainger

Q. What kind of clinical research and therapies are UVA conducting that connect with the basic research?

Netland: We have looked at many of the vision-threatening eye problems in our aniridia patients. We have also found that their mutation is linked with obesity, and have performed clinical trials to evaluate the causes of this. We have performed studies to better understand the mechanisms for some of their clinical problems, such as glaucoma.

We are excited about precision medicine trials identifying patients who can benefit from a specific gene-based therapy and we recently completed a two-year clinical trial evaluating targeted gene therapy. In parallel, similar problems are under study in the frog to complement and build on the work with human patients.

Q. What future do you see for patients with eye disease as this research moves forward?

Netland: We are working with patients with known mutations of a specific gene, so naturally we are excited about precision medicine approaches to these patients. We believe that genetic-based approaches will continue to increase understanding of these diseases and will provide the basis for rational therapy for affected patients, and more broadly for others in the general population who are suffering from the same clinical problems. We believe that new imaging techniques will produce new insights in this area.

Grainger: In the frog, our lab has developed a method for efficiently creating exact patient mutations, again amplifying the opportunities for an integrated approach to precision medicine. There are opportunities with in situ gene modification and other gene-based therapies for addressing problems and improving the quality of life of patients.

Continued here:
Patients, Physicians and Researchers Gather to Probe Genetic Eye Disorders - University of Virginia

In celebration of our 15 Year Anniversary, Academic Editor Ronald CW Ma highlights advancements published in PLOS Medicine in diabetes research and care, including improved precision medicine.

Happy 15th Birthday to PLOS Medicine! I still remember reading about the PLOS journals and the idea of making science accessible to all back when PLoS was first launched. It is amazing how far the Open Access movement has developed, how far that idea has advanced and how scientific publishing has been revolutionized. Congratulations PLOS Medicine on this important milestone!

Among the many articles that I have enjoyed reading in PLOS Medicine over the years, I would like to highlight two for sharing with other readers on this special occasion.

1) Event Rates, Hospital Utilization, and Costs Associated with Major Complications of Diabetes: A Multicountry Comparative Analysis

This paper by Philip Clarke and colleagues from the ADVANCE Collaborative Group, published back in 2010, highlighted the significant economic burden of diabetes and rates of hospitalization resulting from diabetes co-morbidities, using data from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) study, a landmark multi-centre trial on the treatment of diabetes conducted in 20 countries. Within the ADVANCE trial settings, the study demonstrated important differences in the rates of hospitalization for different diabetes complications in different regions of the world (Asia, Eastern Europe, and established market economies such as Australia, New Zealand and Canada), mirroring epidemiological observations of comparative higher nephropathy rates, higher stroke risk, and lower risks of coronary artery disease among Asians (mostly from Chinese centres in this particular trial) with type 2 diabetes, thereby highlighting the heterogeneity of risk of diabetes complications (and costs) in different populations.

This study also provided important tools to facilitate estimation of healthcare expenditure associated with diabetes in different healthcare settings. At the time of the study, it was estimated that the average annual per capita health expenditure was approximately 216 international dollars in China, and 698 international dollars in Russia, but that the annual hospital costs for people with diabetes experiencing major macrovascular complications such as coronary or cerebrovascular events would be around four and ten times these average per capita expenditures. Perhaps not fully appreciated at the time was the significant burden associated with hospitalization with heart failure, which is a topic of much current interest in relation to recent advances in the treatment of type 2 diabetes.

Although the work was focused on evaluating the economic burden of diabetes in different parts of the world, this work can be considered as an important example of early attempts to deconstruct the heterogeneity of type 2 diabetes. As the diabetes epidemic continues unabated, the healthcare burden of diabetes complications has become a major concern globally.

2) Type 2 diabetes genetic loci informed by multi-trait associations point to disease mechanisms and subtypes: A soft clustering analysis

The second article, by Jose Florez and colleagues, utilized a state-of-the-art multi-omics approach to use available genetic and epigenomic data to probe the issue of heterogeneity of diabetes. The authors showed that identified genetic loci linked to diabetes can be segregated according to underlying biological mechanisms which can be used to classify individuals, to provide a way forward for individualized diagnosis, monitoring and treatment. The study highlighted the potential role of genetic variants related to the beta cell, pro-insulin, obesity, lipodystrophy and liver/lipid traits in accounting for different patient characteristics, as well as long-term diabetes outcomes.

What was particularly interesting is the soft-clustering approach adopted by the authors, which did not require genetic variants to fit into only one pathway, or for individuals to be classified to have diabetes due to only one specific pathophysiological defect, but instead, for individuals to be identified to have scores in each of the above-mentioned categories, and thereby accepting that individuals may have developed diabetes with different contribution from the different underlying pathophysiology. The use of such genetic risk scores may be useful in selecting the most appropriate therapies for individualized care in the future.

Over the last 15 years, the global burden of diabetes has more than doubled, from less than 200 million people affected back in the early 2000s to now more than 422 million people affected globally (with the majority in LMICs). These 2 articles represent important advances in our understanding of type 2 diabetes over the last decade. Whilst the ADVANCE study was a landmark study that generated much interest, the Clarke paper highlighted much of the burden of diabetes complications, and our lack of understanding regarding the heterogeneity in risk of diabetes complications. Together with the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Veterans Affairs Diabetes Trial (VADT) studies, these landmark studies, published between 2008-2010, have highlighted the potential dangers of hypoglycaemia, and heralded the debate and call for more individualized treatment in type 2 diabetes, and contributed to the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) to propose in their joint position statement on management of hyperglycaemia in type 2 diabetes in 2012 to move away from a one-size-fit-all approach to treatment, but instead adopt a treatment strategy that is more tailored to individual patient profile, disease duration, co-morbidities and expectations. This represented a major watershed moment in the evolution of diabetes research and care.

With recent advances in genomic medicine and the genetics of type 2 diabetes, some of which have been reported in PLOS Medicine, the era of precision medicine in diabetes is very much here to stay. We, as diabetes researchers and clinicians caring for people with diabetes, look forward to further advances in our understanding of how best to treat individuals with diabetes based on their underlying genetics, pathophysiology, and needs, and to improving outcomes for people with diabetes.

Congratulations again PLOS Medicine and we look forward to the next 15 years of exciting advances!

Ronald Ma is Professor and Head of Division of Endocrinology and Diabetes at the Department of Medicine and Therapeutics, The Chinese University of Hong Kong, and co-lead of the Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine. He is a member of the Executive Board, Asian Association for the Study of Diabetes (AASD), and member of the editorial board of PLOS Medicine.

Acknowledgement: RCWM acknowledge support from the Hong Kong Research Grants Council Research Impact Fund (R4012-18).

Image Credit: stevepb, Pixabay (CC0)

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Charting the evolution of diabetes research and care | Speaking of Medicine - PLoS Blogs

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Beam Therapeutics, a biotechnology company developing precision genetic medicines through base editing, today announced that it has entered into a collaboration and license agreement with a newly-formed company, Prime Medicine, Inc. to research and develop a novel gene editing technology called prime editing, recently developed by one of Beams co-founders, David Liu, Ph.D., and his group at the Broad Institute of Harvard and MIT.

Under the agreement, Beam has the exclusive right to develop prime editing technology for the creation or correction of any single-base transition mutations, as well as for the treatment of sickle cell disease, both of which Beam is already pursuing with its base editing technology. Transition mutations (e.g. A to G, C to T) are the largest single class of disease-associated genetic mutations, and are also potentially treatable with base editing. Beam plans to evaluate prime editing technology for potential use in future programs.

Part of Beams strategy is to continue to access emerging technologies in gene editing and delivery, while finding new ways to create meaningful options for patients. Our collaboration with, and contribution to the formation of, Prime Medicine is a great example of that approach, allowing us to incorporate prime editing into the Beam platform, said John Evans, chief executive officer of Beam. This partnership enables both companies to advance the technology in distinct spaces, with Beam focusing on the kinds of edits that are most similar to our base editing technology.

As part of the collaboration, Beam is providing initial interim leadership to Prime Medicine for the first year of the collaboration, and will have the right to designate a member on Prime Medicines board. The parties will also grant each other non-exclusive licenses to certain CRISPR technology and delivery technology to enable the development of prime editing products.

About Beam Therapeutics

Beam Therapeutics is developing precision genetic medicines through base editing. Founded by leading scientists in CRISPR gene editing, Beam is pursuing therapies for serious diseases using its proprietary base editing technology, which can make precise edits to single base pairs in DNA and RNA. Beam is headquartered in Cambridge, Massachusetts. For additional information, visit http://www.BeamTx.com.

Originally posted here:
Beam Therapeutics Announces Collaboration and Exclusive License Agreement with Prime Medicine for Prime Editing Technology - Business Wire

Your genes can effect how you respond to medicine. Genetic testing can help identify the right drug at the right dose for a patient. Courtesy of Mayo Clinic

Predicting whether a patient like KerriePrettitorewill have a fatal reaction to a chemotherapy drug or even whether adrugwill work at all is the future of medicine, and its coming soon.

Genetic testing can help predict how patients will respond to a drug,whether its designed to combat cancer or other illnesses. Eventually, that will enable doctors to individualize patient treatment, choosing a medication and dose to best match a patients genetic profile. The goal is to maximize benefit while minimizing harm.

Research inseveral areasalready is having an impact:

KerriePrettitore, a Ridgewood woman,suffered from a genetic abnormality called DPD deficiency, which prevents someone from breaking down the chemotherapy drug 5-FU, or fluorouracil.Agenetic test can help identify patients who may be at risk of developing such a reaction.

Frances national drug-regulating agency began recommending last year that all patientsprescribed5-FU and related drugs be screened for DPD deficiency beforehand. Two hundred people a year die in France because they receive the drug and have DPD deficiency, according to a company that performs such tests. The company recommends that the genetic test be combined with a blood test for maximum accuracy, a practice that has been used in the Netherlands for almost a decade.

In theUnited States, testing for DPD deficiency is not currently recommended by major cancer treatment organizations.But some scientists say change will come soon.

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Genetic testsmust be inexpensive,produce results quickly and provide clinically useful informationto be cost-effective, said RobertDiasio, an authority on DPD deficiency and director of the Mayo Clinic Cancer Center. The tests currently availablefor DPD deficiencydont yet meet that standard, he said.

The testsdont identify everyone atrisk,and they may identify a mutation in a person who turns out to be able to tolerate the drug, he said. Thats because they test for only a handful of mutations. They dont testfor all possible mutations because it is expensive andyieldsinformation that scientists dont yet know how to interpret.

But the cost of a complete genetic analysis is coming downandthe turnaround time is getting quicker, he noted. Moreknowledge is needed, however,about which mutations are important and which are irrelevant to doctorsmakingprescribing decisions,Diasiosaid.

At the Mayo Clinics Center for Individualized Medicine,astudy of 10,000 Minnesota patientsis underway. It will integratepatients genetic informationinto theirelectronic medical recordsto inform physicians about significant linkages when certain medications are prescribed.

As research advances, more linkages will be discovered and included in the individual records. The goal isto help patients get the right drug at the right dose for their disease personalized medicine at its best.

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Soon, genetic testing for cancer treatment could match you with the perfect drug - NorthJersey.com

When the UK Life Sciences Champion Sir John Bell recently highlighted the need to create new industries within life sciences, Carina Healy immediately saw the potential for Scotland.

When the UK Life Sciences Champion Sir John Bell recently highlighted the need to create new industries within life sciences, Carina Healy immediately saw the potential for Scotland.

Sir John, speaking at the Medicines and Healthcare Products Regulatory Agency, identified genomics, digital health and early diagnosis as three areas where the UK could develop new industries and remain a world leader in life sciences.

Healy, a partner and life sciences specialist with international legal firm CMS, says: These areas play into what we do well in Scotland and present very big opportunities. Healy goes on to explain these new industries and the potential they hold for Scotland.

Genomics using genotyping to inform how patients are treated is closely linked to precision or stratified medicine, where Scotland is already excelling.

Precision medicine allows doctors to tailor treatments to each patients specific needs, which can save lives, avoid unpleasant side-effects caused by unsuitable treatments and save the NHS money.

Scotland has great expertise in this area, with world-class academic research and cutting-edge companies developing new treatments to benefit the NHS. This is backed by innovative initiatives such as the Stratified Medicine Scotland Innovation Centre based at the Queen Elizabeth University Hospital (QEUH) in Glasgow, which brings together specialists from across academia, industry and the NHS.

One challenge facing this new industry is how to use the wealth of genetic data now available to inform medical treatment. Although genetic testing is getting increasingly more affordable, further research is needed to link that genetic data to specific diseases and treatment options.

As Healy explains: The technology is there, but it doesnt tell you much yet. However, in areas like breast cancer, the use of the BRCA and HER-2 biomarkers is well-established and gives a clear indication of whether a certain class of patient is at risk or will respond to a specific drug like Herceptin.

Healy says that, in the hospital of the future, an individuals genetic profile is likely to be available in the same way as access to, for example, an individuals blood type. She says: Were still quite far away, but weve decoded the genome and can do it cost-effectively. With further research we will be able to know how to make best use of this data to deliver more effective health care for individual patients.

A UK government science and innovation audit of precision medicine in Scotland this year, led by the University of Glasgow, highlighted the significant assets Scotland has in this field and their potential. It suggested the effective use of electronic health records could drive collaboration and help turn academic research and innovation into better clinical practice.

Healy says the universitys bid for a Strength in Places grant to create a Living Laboratory for precision medicine at QEUH is an excellent example of how Scotland can bridge the gap between genomics research and patient benefit.

Digital health, which uses software, mobile apps and digital technology for health purposes, is an area where Healy thinks Scotland has work to do but has all the key skills in place to make real progress.

We have real strength in informatics, data science and AI in our academic research institutions, she says. Although we need to integrate those sectors better with life sciences and healthcare. The potential is there to build real capacity and deliver tangible patient benefits.

In terms of digital health, this means making healthcare more efficient through use of digital technology, and improving the patient-facing offering.

Scotland has great assets in the IT sector generally, from Silicon Glen to the burgeoning technology scene in Edinburgh. The capital is set to receive further investment in technology infrastructure as part of the 1.3 billion Edinburgh City Region Deal, which will focus on data-driven innovation and help boost Scotlands existing capabilities.

The key to realising Scotlands potential in the new digital health industry will be in linking the countrys digital expertise with its life sciences expertise to create new solutions. Work to link Scotlands technology and life sciences industries has already begun. Exscientia, a company founded in Dundee, has been at the forefront of using digital technology to improve the drug discovery process, resulting in several collaborations this year with big-name drugs companies.

Further collaboration between the two industries will be supported by Glasgows Industrial Centre for Artificial Intelligence Research in Digital Diagnostics iCAIRD which involves 15 partners from across academia, industry and the NHS.

Healy stresses that although collaboration between private companies and the NHS has huge potential benefits, these collaborations must be structured correctly. It is especially important to address ethical and legal issues in accessing and managing patients data.

The collaboration between Googles DeepMind and Londons Royal Free Hospital, which involved the transfer of personal data of 1.6 million patients, was an example of a collaboration that was not structured correctly and was found to be in breach of data protection laws. Healy says: This erodes public trust in these types of initiatives, despite the very obvious benefits in healthcare treatment that can be generated.

Despite this setback, DeepMinds Streams app is now in use at the Royal Free Hospital and has been shown to enable consultants to treat acute kidney injury faster, potentially saving the NHS on average 2,000 per patient and saving consultants up to two hours per day.

The great advantage for Scotland is that we have one NHS. We can access data sources more easily and we can pool it more effectively, says Healy. However, practices can vary across different hospitals and trusts, and clear central guidance would be helpful to ensure data is used both ethically and effectively.

There are also issues around data quality as it is, of course, collected for clinical purposes, not for research or for training artificial intelligence systems.

The ultimate goal is to pool data for patient benefit, and to structure collaborations between private companies and the NHS carefully so personal data is managed appropriately.

There are also potential societal and political issues around ensuring all patients can benefit from digital health initiatives, for example in areas like GP surgery triage. Systems such as Babylon and DrDoctor allow patients remote access to GP services, but often benefit specific groups rather than the whole population.

Younger, more IT-literate patients who have a specific issue but are generally healthier tend to use systems like this, while older, less IT-savvy patients with chronic conditions still go to GP surgeries, says Healy. So GP surgeries are left with patients who need more care and time, but the funding per patient is the same. The digital health gap between different generations will close over time, but it is still quite wide now.

Overall, Healy notes, the message is that digital health offers huge opportunities in Scotland:

We need to encourage more health tech businesses to work with the NHS in Scotland and get more entrepreneurs looking at this area. There are big opportunities for new entrants.

In the third new life sciences industry, early diagnostics, Healy also sees a huge area of unmet need and opportunity in Scotland. She cites image recognition AI, where, for example, training an artificial intelligence system using large numbers of CT scans can mean tumours are spotted more quickly and accurately than using a surgeons eye, leading to earlier diagnosis, which in turn means more successful treatment for patients and potential savings for the NHS.

Scottish-based companies, including Canon Medical Research Europe, are exploring how technology such as AI can help with early diagnosis. Canons research, supported by the Scottish Funding Council, is looking for innovative ways to diagnose and measure mesothelioma tumours, which are particularly difficult to measure and treat.

Collaborations between Scottish companies and the NHS which capitalise on the organisations pool of health data will be a big boost to research and development of early diagnostics, particularly with the help of AI.

Although Healy recognises the challenges in collaborating on such projects, she is positive about the future: It can still be hard to break down NHS silos and work through its contracting processes. However, Scotlands strength is underpinned by excellent collaboration between the NHS, academia and industry. You can see it working in projects like iCAIRD and the QEUHs Clinical Innovation Zone.

Healy sees this as a good reason for Scotland to be positive about its life sciences industry and its opportunity to make the most of Sir Johns three new industries genomics, digital health and early diagnostics. It all comes back to that strong, deep collaboration. We need to build on that and keep selling Scotlands strengths to a wider global marketplace.

Our academic base is really strong, we have one NHS with very good electronic health records and the ability of industry to collaborate across different academic and NHS bodies to deliver positive patient outcomes.

Find out more at CMS.

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CMS on how life sciences advancements are improving patient care - The Scotsman

A blood test that measures the amount of cell-free DNA (cfDNA) in the bloodstreamcalled a liquid biopsycorrelates with how patients will progress after they are diagnosed with glioblastoma (GBM), the deadliest and most common primary brain tumor in adults

In a new study, researchers from theAbramson Cancer Center are the first to show that patients with a higher concentration of cfDNAcirculating DNA that cancer and other cells shed into the bloodhave a shorter progression-free survival than patients with less cfDNA, and that cfDNA spikes in patients either at the time of or just before their disease progresses. The team also compared genetic sequencing of solid tissue biopsies in GBM side-by-side with the liquid biopsies and found that while both biopsies detected genetic mutations in more than half of patients, none of those mutations overlapped, meaning liquid biopsy may provide complementary information about the molecular or genetic makeup of each tumor.Clinical Cancer Research, a journal of the American Association for Cancer Research,published the findings.

Doctors have begun using liquid biopsies more frequently to monitor certain cancersparticularly lung cancerin recent years as research has shown their effectiveness in other disease sites. But until now, there has been little focus on the clinical utility of liquid biopsy in brain tumors, said the studys senior authorErica L. Carpenter, director of the Liquid Biopsy Laboratory and a research assistant professor of medicine.

The findings may eventually prove impactful for GBM patients. The disease is particularly aggressive, and while most estimates show there are around 11,000 new cases each year, the five-year survival rate is between 5and 10 percent.

Read more at Penn Medicine News.

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Blood test can predict prognosis in deadly brain cancer - Penn: Office of University Communications

Healthcare, which has been the second-worst performer among the 11 major S&P 500 sectors this year, took the center stage this month with some outperformance compared to other sectors. This is especially true against the backdrop of positive news flow, including trial results and deal activities. Better-than-expected corporate earnings added to the strength.

Flurry of News Flow

Biogen BIIB has spread optimism into the broad healthcare sector following its Alzheimer treatment report. The biotech company decided to move forward with the approval of aducanumab, a treatment for early Alzheimers diseases, after the drug met the primary endpoint of a Phase 3 Emerge study. If approved, Biogens drug would be the first to slow cognitive decline in Alzheimers patients, a milestone in long-running efforts to find a medicine that can treat the memory-robbing disease.

Hepion Pharmaceuticals HEPA also led the sector higher following data that showed potential for its CRV431 as a drug candidate for liver disease treatment. A pan-cyclophilin inhibition, CRV431, is well suited to address multiple therapeutic needs that are currently either underserved, or completely absent. It reduces fibrosis and tumor development in chronic liver disease models (read: Biotech ETFs Surge on a Flurry of Positive News).

Additionally, Alexion Pharmaceuticals ALXN, which joined the ongoing M&A wave in the pharma/biotech sector, added to the strength in the space. The company agreed to acquire a clinical-stage biopharmaceutical company Achillion Pharmaceuticals ACHN for $930 million in a move to expand its pipeline of rare disease treatments. Under the terms of the deal, Alexion will pay $6.30 for each Achillion share outstanding, which is 73% higher than the Oct 15 closing price. The deal also includes potential for an additional payment for Achillion shares in the form of contingent value rights (CVRs) to be paid if certain clinical and regulatory milestones are achieved. The transaction is expected to close in the first half of 2020, subject to approvals, including from Achillion shareholders.

Solid Earnings

A solid Q3 earnings report from Biogen also drove the stock price and the sector higher. The biotech company beat estimates for both earnings and revenues. Pharma giants Merck MRK and Pfizer PFE came up with an earnings beat and raised their financial forecast. Upbeat results from the duo have raised hopes about Big Pharmas prospects even as politicians focus on health-care costs ahead of the 2020 election (read: What's in Store for Healthcare ETFs in Q3 Earnings?).

Given this, we highlight six healthcare ETFs that are leading the way higher in October.

Virtus LifeSci Biotech Clinical Trials ETF BBC Up 13.3%

This fund has a novel approach to biotechnology investing with exposure to companies that are in the clinical trial stage. This can easily be done by tracking the LifeSci Biotechnology Clinical Trials Index. BBC has amassed $23.6 million in its asset base and charges 79 bps in fees per year from its investors. It trades in a light average daily volume of around 4,000 shares and holds 95 securities in its basket with each accounting for no more than 2.7% share. The product carries a Zacks ETF Rank #3 (Hold) with a High risk outlook.

ALPS Medical Breakthroughs ETF SBIO Up 13%

This fund provides exposure to companies with one or more drugs in Phase II or Phase III FDA clinical trials by tracking S-Network Medical Breakthroughs Index. It holds 78 securities in its basket with none accounting for more than 5.1% share. The product charges 50 basis points in fees per year from investors and trades in a moderate average daily volume of about 34,000 shares. It has AUM of $171.4 million in its asset base and has a Zacks ETF Rank #3 with a High risk outlook (read: Top-Performing Biotech ETFs YTD).

SPDR S&P Pharmaceuticals ETF XPH Up 10.7%

This fund provides exposure to pharma companies by tracking the S&P Pharmaceuticals Select Industry Index. With AUM of $184.4 million, it trades in good volume of around 69,000 shares a day and charges 35 bps in fees a year. In total, the product holds 39 securities with none accounting for more than 5.71% of assets. It has a Zacks ETF Rank #3 with a High risk outlook.

iShares U.S. Healthcare Providers ETF IHF Up 10.3%

This ETF follows the Dow Jones U.S. Select Healthcare Providers Index with exposure to companies that provide health insurance, diagnostics and specialized treatment. In total, the fund holds 49 securities in its basket with each making up for no more than 23.3%. The fund has amassed $790.4 million in its asset base, while volume is moderate at about 79,000 shares per day on average. It charges 43 bps in annual fees and has a Zacks ETF Rank #3 with a Medium risk outlook (read: Healthcare ETFs to Buy on UnitedHealth's Solid Q3 Earnings).

SPDR S&P Biotech ETF XBI Up 10.1%

With AUM of $3.8 billion, XBI provides equal-weight exposure of around 2% across 117 biotechnology stocks by tracking the S&P Biotechnology Select Industry Index. It has 0.35% in expense ratio and trades in an average daily volume of 4.6 million shares. The fund has a Zacks ETF Rank #2 (Buy) with a High risk outlook.

Global X Genomics & Biotechnology ETF GNOM Up 10.1%

This is a new entrant in the space having accumulated $15.3 million since its inception on Apr 5. It seeks to invest in companies that potentially stand to benefit from further advances in the field of genomic science, such as companies involved in gene editing, genomic sequencing, genetic medicine/therapy, computational genomics and biotechnology. The product follows the Solactive Genomics Index, charging 68 bps in annual fees. It holds 42 stocks in its basket with each accounting for less than 6.8% shares. GNOM trades in average daily volume of 4,000 shares (read: ETFs to Gain From the Booming Genomics Market).

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A genetic test showing how people respond to common medicines has the potential to revolutionise the way doctors prescribe drugs. Business editor Maria Slade reports.

Sleeping has never been my strong suit. Throughout my adult life Ive tried everything from hypnosis and hot milk to yoga and the droning narrations of the History Channel, with varying degrees of success.

Ive also tried drugs, of course, but doctors are generally pretty dark on handing out sleeping pills. After two decades of intermittent insomnia my GP and I have come to an understanding: he will give me melatonin for everyday use, and a tiny handful of Zopiclone in extreme circumstances, eg economy air travel.

Who would have thought cruciferous vegetables could upset that carefully balanced equilibrium? For it turns out I am an ultrarapid metaboliser of melatonin, a fast processor of the sleep regulating hormone, particularly if I smoke or eat a lot of broccoli and cauliflower.

I know this because Ive had my DNA tested to see how I respond to a raft of common medicines. With the swab of a cheek Waikato-based Pinnacle Ventures myDNA test can detect how well I metabolise around 60% of the most regularly prescribed medications, including statins, antidepressants and anti-inflammatories.

Tests like myDNA are moving healthcare away from a one-size-fits-all approach and reducing the trial and error often associated with prescribing new medicines. The new tools have the potential to save the nation millions on the annual drugs bill, not to mention improve health outcomes.

Known as pharmacogenomics, the science is well established but the medical profession is only now starting to get on board with the benefits it can provide. While knowing to avoid too much broccoli when taking melatonin is a small outcome for me, for other people the ramifications of their genetic makeup can be far-reaching. Some antipsychotic medications fall into the same CYP1A2 gene category as melatonin which has implications for schizophrenic patients, Pinnacle Ventures medical director Dr Kerry Macaskill-Smith says.

Most of them smoke, so you have to give them quite a lot of medicine to get it working. And if they quit smoking their medicine level is going to build up and possibly go to toxic levels. If we know this we can monitor you much more closely.

Macaskill-Smith isnt advising me to cut brassicas out of my diet. The key is my GP possessing the information about how I react to medications and being able to prescribe accordingly. Pinnacle Ventures is in the process of integrating myDNA with health records software programmes so that the test results can be sent directly to healthcare providers, for two important reasons: to protect patient information, and to prevent people from misinterpreting the results.

Pinnacle Ventures medical director Dr Kerry Macaskill-Smith (Photo: Supplied.)

The myDNA test doesnt look at any disease-risk genetic information, so it wont tell you whether you might get cancer, for example. I personally think thats quite a good thing, because what do you do with that information? Macaskill-Smith asks. It also wont tell you whether youre related to the British royal family or descended from vikings. It is specifically designed to look at your reaction to medicines, and the information isnt used for anything else.

The test results follow a traffic light system green for medications that will behave more or less normally in your body, amber for ones with minor prescribing considerations, and red where theres more of an issue. My melatonin/broccoli sensitivity fell into the red category. Statins have an amber-level adverse effect on me, in that some brands are more likely to cause me muscle pain, and I also have a reduced response to opioid pain relievers which comes as no surprise given a family history of funny reactions to morphine.

Everybodys got something, Macaskill-Smith says. Its very unusual for a person to get all the way through their report without having something they can take action on or something that would affect their future prescribing, weve found. It can save six weeks to three months of mucking around trying to get a medication right, for instance with antidepressants where it takes a cycle to see how it works, she says.

Once youve got a persons genetic test you can treat them on the basis of their genetic profile and not on the law of averages. I can see a future where everybody has one of these tests done to help inform their future medications.

Pinnacle Ventures is part of the Pinnacle Group, a network of primary and community healthcare provides across the central North Island. Ultimately its aim is to build up the body of data around the New Zealand DNA, and it is partnering with key iwi groups, Auckland and Otago Universities, and the governments innovation agency Callaghan Innovation to develop a better understanding of how this countrys unique populations respond to different medications.

Auckland University pharmacogenomics expert Nuala Helsby says sending these test results directly to a health practitioner is the right approach.

Your genes are just one part of the story, and there is so much more going on with everything that you interact with in your environment. The whole of that process is what anyone whos prescribing has to think about all the time. Its the art of medicine.

Overseas, ancestry sites such as 23andMe also offer medical information, she says. They will genotype you, and certainly in the States I believe they can give you a health report on that. The problem is its too broad; you need the nuance of having the medical practitioner sat with you taking everything else into account.

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What I learned that broccoli can do to me when I got my DNA tested - The Spinoff

Nathaly Sweeney, a neonatologist at Rady Children's Hospital-San Diego and researcher with Rady Children's Institute for Genomic Medicine, attends to a young patient in the hospital's neonatal intensive care unit. Jenny Siegwart/Rady Children's Institute for Genomic Medicine hide caption

Nathaly Sweeney, a neonatologist at Rady Children's Hospital-San Diego and researcher with Rady Children's Institute for Genomic Medicine, attends to a young patient in the hospital's neonatal intensive care unit.

When Nathaly Sweeney launched her career as a pediatric heart specialist a few years ago, she says, it was a struggle to anticipate which babies would need emergency surgery or when.

"We just didn't know whose heart was going to fail first," she says. "There was no rhyme or reason who was coming to the intensive care unit over and over again, versus the ones that were doing well."

Now, just a few years later, Sweeney has at her fingertips the results of the complete genome sequence of her sickest patients in a couple of days.

That's because of remarkable strides in the speed at which genomes can be sequenced and analyzed. Doctors who treat newborns in the intensive care unit are turning to this technology to help them diagnose their difficult cases.

Sweeney sees her tiny patients in the neonatal intensive care unit of Rady Children's Hospital in San Diego. Doctors there can figure out what's wrong with about two-thirds of these newborns without a pricey DNA test. The rest have been medical mysteries.

"We had patients that were lying here in the hospital for six or seven months, not doing very well," she says. "The physicians would refer them for rapid genome sequencing and would diagnose them with something we didn't even think of!"

Rady's Institute for Genomic Medicine, which has been pioneering this technology, has now sequenced the genomes of more than 1,000 newborns.

In a building across the street from the hospital, three $1 million sequencing machines form the core of the operation. Technicians tending to the NovaSeq 6000s can put DNA from babies (and often their parents) into the machine in the late afternoon and have a complete genome sequence back by 11 a.m. or noon the next day, says clinical lab scientist Luca Van der Kraan.

That fact is worth repeating: An entire genome is decoded in about 16 hours.

Kasia Ellsworth is one of the experts waiting in a nearby office to analyze the information. That task has shrunk from months to typically just four hours, thanks to increasingly sophisticated software.

Ellsworth inputs the baby's symptoms into the software, which then spits out a long list of genetic variants that might be related to the illness. She scrolls down the screen.

"I'm looking through a list of those variants and then basically deciding whether something may be truly contributing to the disease or not," she says.

About 40% of the time, a gene stands out, giving doctors a tentative diagnosis. Follow-up tests are often requested, and those can take several days. But in the meantime, doctors can sometimes act on the information they have in hand.

When she or a colleague makes a diagnosis, "You always feel very relieved, very happy and excited," she says. "But at the same time you kind of need to put it in perspective. What does it mean for the family, for the patient, for the clinician as well?"

Often it's a sense of relief. And for a minority of cases, it can affect the baby's treatment.

"We now are at the point where I think the evidence is overwhelming that a rapid genome sequence can save a child's life," says Dr. Stephen Kingsmore, the institute's director and the driving force behind this revolution.

By his reckoning, the results change the way doctors manage these cases about 40% of the time.

Treatments are available for only a small share of these rare diseases. In other cases, the information can help parents and doctors understand what's wrong with their baby even if there is no treatment or learn whether death is inevitable. "And there it's a very different conversation," Kingsmore says. "We help guide parents through picking an appropriate point at which to say enough is enough" and to end futile treatments.

Of course, Kingsmore highlights the happier outcomes. One example is a bouncy girl named Sebastiana, now approaching her third birthday.

As a newborn, Sebastiana Manuel was diagnosed with a rare disease after rapid genome sequencing. She is seen here at 11 months of age. Jenny Siegwart/Rady Children's Institute for Genomic Medicine hide caption

As a newborn, Sebastiana Manuel was diagnosed with a rare disease after rapid genome sequencing. She is seen here at 11 months of age.

He showed off her case recently in front of the Global Genes conference, a meeting of families with rare genetic conditions.

"She was critically ill in our intensive care unit," he tells the audience, "and in a couple of days we gave the doctors the answer. It's Ohtahara syndrome. It comes with this specific therapy. And she hasn't had a seizure in 2 1/2 years. She doesn't take any medication."

The audience applauds enthusiastically at an outcome that sounds miraculous. But when you meet Sebastiana and her mother, Dolores Sebastian, a more complicated story emerges.

Ohtahara syndrome isn't actually what made Sebastiana ill it's a term doctors use to describe newborn seizures. Those are actually a symptom of deeper brain issues. That was apparent the day she was born.

"She was acting weird and screaming and crying and turning purple and we weren't sure why," her mother says.

The hospital where Sebastiana was born rushed her to the neonatal intensive care unit, across town at Rady. She was having frequent seizures. The following days were a nightmare for Sebastian and her husband.

"I can't even describe it," she says. "I always keep on saying that at that moment I was kind of like dead, but I was walking."

The hospital ran a battery of tests to look for severe brain damage. They couldn't get to the bottom of it.

"They came in and offered us the genomic testing," Sebastian said. "They never told us how quick it would be."

She was surprised when the results were back in four days. The doctor told her they had identified a gene variant that can trigger seizures as well as do other harm to the brain.

"He said this is how we're going to go ahead and change her medications now and treat her," she says. And that made a "huge difference, [an] amazing difference."

Sebastiana was already on a medication that was helping control her seizures, but they sedated her to the extent that she needed a feeding tube. On the new medication, carbamazepine, she was alert and able to eat, and her seizures were still under control. Sebastian says her daughter is still taking that drug.

Controlling her seizures isn't a cure. Children who have this genetic variant, in a gene called KCNQ2, can have a range of symptoms from benign to debilitating. Sebastiana falls somewhere in between. For example, she has only a few words in her vocabulary as she approaches the age of 3.

"She took her first steps when she was 2 years old, so she's delayed in some things," Sebastian says, "but she's catching up very quickly. She has [physical therapy]; she's going to start speech therapy. She gets a lot of help but everything's working."

Sebastiana Manuel (second from left) with members of her family: Domingo Manuel Jr. (from left), Dolores Sebastian and Tony Manuel. Jenny Siegwart/Rady Children's Institute for Genomic Medicine hide caption

Sebastiana Manuel (second from left) with members of her family: Domingo Manuel Jr. (from left), Dolores Sebastian and Tony Manuel.

KCNQ2 variants are the most common genetic factor in epilepsy, causing about a third of all gene-linked cases and about 5% of all epilepsies. Sebastiana's case could have been diagnosed with a less expensive test. For example, Invitae geneticist Dr. Ed Esplin says his company offers a genetic screen for epilepsy that has a $1,500 list price and a two-week turnaround.

Rady's whole-genome test costs $10,000, Kingsmore says. But it casts a wider net, so it might provide useful information if a baby's seizures are caused by something other than epilepsy.

And Kingsmore says his test costs about as much as a single day in the NICU. "In some babies we avoid them being in the intensive care unit literally for months," he says.

Kingsmore and colleagues have published some evidence that their approach is cost-effective, based on an analysis of 42 cases.

Even so, most insurance companies and state Medicaid programs are still balking at the cost. Kingsmore says private donors are helping support this effort at Rady, which sequences about 10% of the babies in the NICU, and at more than a dozen others scattered from Honolulu to Miami. They send their samples to Rady for analysis.

Kingsmore is pushing to expand his network in the next few years, to reach 10,000 babies at several hundred children's hospitals.

Other providers are also starting to offer whole-genome sequencing. But Dr. Isaac Kohane, chair of the department of biomedical informatics at Harvard Medical School, worries that the technology is too unreliable.

Knowledge of genes and disease is evolving rapidly, so these analyses run the risk of either missing a diagnosis or making a mistaken one. Kohane says there's still a lot of dubious information there a typical person has 10 to 40 gene variants that the textbooks incorrectly identify as causing disease.

Kohane is part of a medical network that helps diagnose people with baffling diseases. A study from 2018 found "a third of the patients who actually come to us already had full genome sequences and interpretations," Kohane says. "They were just not correct."

Even so, Kohane sees this use in the NICU as a relatively fruitful use of gene sequencing. "This is one of the few areas where I think the Human Genome Project is really beginning to pay off in health care," he says, "but buyer beware, it's not something ready to be practiced in every hospital." (He supports the work at Rady in fact, he is a science adviser.)

Kingsmore is already looking ahead. "We want to solve the next bottleneck, which is, 'I don't have a great treatment for this baby,' " he says. That's a far greater challenge, and it's especially difficult for a mutation that has altered a baby's development in the womb. Those problems may often not be reversible.

Kingsmore is undeterred. "It's going to be an incredibly exciting time in pediatrics," he says.

You can contact NPR science correspondent Richard Harris at rharris@npr.org.

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Genome Sequencing In NICU Can Speed Diagnosis Of Rare Inherited Diseases : Shots - Health News - NPR

People should not make health decisions based on genetic tests they do at home, experts have warned.

The University of Southampton team,writing in the British Medical Journal, warn results can be unreliable.

The geneticists said the tests could be wrongly reassuring or lead to unnecessary worry.

23andMe, one of the companies offering tests, said there were many cases where results had prompted further checks and preventative treatment.

Prof Anneke Lucassen, president of the British Society for Genetic Medicine and a consultant in clinical genetics at University Hospital Southampton led the research.

She said: Genetic tests sold online and in shops should absolutely not be used to inform health decisions without further scrutiny.

Finding a health risk via these tests often does not mean a person will go on to develop the health problem in question, while reassuring results might be unreliable.

[T]he BMJ paper warns genetic tests often prioritise breadth over detail, citing a 23andMe test that checks for a few variants of Brca1 and 2, linked to breast and ovarian cancer risk, when there are actually thousands.

A 23andMe spokesman said its processes were extremely accurate and it spelt out exactly what its Brca test looked for.

Read full, original post: Genetic tests: Experts urge caution over home testing

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Consumer genetic tests shouldn't be used to make health decisions, experts warn - Genetic Literacy Project