Category Archives: Genetic medicine

New testing at the University of Vermont Medical Center will help determine the role DNA plays in your health.

We want to improve peoples lives, said Dr. Debra Leonard, chair of Pathology and Laboratory Medicine at the University of Vermont Medical Center.

For the past year and a half, shes been working along with a team of physicians and specialists to develop Genomic DNA Testing.

It really is to integrate genetic information into routine medical care, she said.

Dr. Leonard said that information can be very helpful in improving outcomes for patients if they know their disease risk in advance. The testing will allow patients to learn about differences in their DNA that can make certain diseases more likely.

What we will be focusing on is diseases related to the heart and diseases related to cancer risk, Dr. Leonard said.

UVM Health Network is partnering with Invitae and LunaPBC on the project which will provide information on nearly 150 genes that are indicators for illnesses. The goal is to recognize if a patient is at risk for one of those diseases before they actually experience their first symptom, allowing doctors to intervene early and make informed decisions.

So we can use preventive strategies or close monitoring to catch the diseases earlier or even implement strategies to prevent the diseases, she said.

Right now, the testing is in its beginning phases. Last Friday, it was offered to the first patient, who agreed to have their blood drawn and sent out for testing, fully funded by the department. Over the next year, UVMMC is aiming to test 1,000 patients ages 18 and older.

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Genetic testing at UVMMC aims to improve patient care - Local 22/44 News

Summary

A study reports on a new way to determine who is most likely to benefit from immunotherapy. It may help explain why immunotherapy works differently in people around the world.

Since 2011, the immunotherapy drugs called checkpoint inhibitors have become an increasingly important treatment for certain cancers. This is especially true for people with melanoma and lung cancer.

Early on, investigators observed that these drugs are extremely effective for some people, even eliminating their cancer entirely. Unfortunately, they dont work at all for many others. Considerable research has tried to understand why this is the case and exactly how these drugs work.

Checkpoint inhibitors work by releasing a natural brake on your immune system so that immune cells called T cells recognize and attack tumors.

Memorial Sloan Kettering physician-scientist Timothy Chan has focused on these efforts. He is one of the corresponding authors of a study published November 7, in Nature Medicine that reports a new way to determine who is most likely to benefit from immunotherapy. The findings may help explain why immunotherapy works differently in people around the world.

Our results help solve part of the mystery of why there is such a large variation in the effectiveness of immune checkpoint drugs, says Dr. Chan, who leads the Immunogenomics and Precision Oncology Platform at MSK. Its important that future clinical trials of immune checkpoint drugs take our discovery into account. This is especially important for international phase III trials.

For decades, the human leukocyte antigen (HLA) genes have been known to govern how the immune system responds to foreign substances in the body. Over thousands of generations, as early humans migrated out of Africa and around the planet, they evolved variations in their HLA genes. These changes protected them from infectious organisms that were found in different parts of the world.

The classic battle between pathogens and the human immune system plays out in the HLA genes, Dr. Chan says. A 2017 study from Dr. Chan was the first to show that HLA genes are important for the bodys ability to see cancer after immunotherapy as well. That study reported that people who had a greater number of different copies, or alleles, in their HLA-1 genes responded better to immunotherapy compared with those whose HLA-1 genes had fewer alleles. The new study builds on this previous work.

To quantify how efficient the immune system is at detecting cancer, the researchers looked at the HLA genes from more than 1,500 people who had received immune checkpoint drugs as part of clinical trials at MSK and other hospitals. Most of those included in the study had melanoma or non-small cell lung cancer, but other kinds of cancer were also represented.

Study Uncovers Genetic Reasons Why Some People Respond to Immunotherapy Better than Others

Immunotherapy drugs called checkpoint inhibitors have been a game changer for some people with cancer. But for most patients, these drugs have been disappointing. Researchers are trying to figure out why.

People inherit one copy of HLA-1 from each parent. For each person analyzed, the team found that the more molecularly diverse, or different from each other, the two copies of each of their HLA-1 genes were, the more likely someone was to respond to treatment and survive their cancer. The investigators developed a novel way to measure this difference, which they call HLA evolutionary diversity (HED).

Dr. Chans co-corresponding author on the Nature Medicine paper, Tobias Lenz of the Max Planck Institute for Evolutionary Biology in Germany, is an expert in the evolution of the human immune system and the HLA genes. Research fellow Diego Chowell and graduate student Chirag Krishna from Dr. Chans lab and graduate student Federica Pierini from Dr. Lenzs lab were the co-first authors.

Dr. Chan has also looked at other factors that make immune checkpoint drugs more effective. In 2014, he led the first studies finding that patients who responded to these drugs tended to have a large number of gene mutations in their tumors. This is known as having a high tumor mutational burden (TMB). When tumors have a greater number of mutations, it is more likely that they will produce proteins that the immune system hasnt seen before.

For checkpoint inhibitor drugs to be effective, the immune system needs to be able to recognize cancer cells as foreign, Dr. Chan says. High TMB and diverse HLA genes are two sides of the same coin. Both make it more likely that the immune system will see the cancer.

The researchers note in their study that high TMB and high HED are independent of each other, but the combined outcome of the two led to benefits from immunotherapy drugs that were greater than either of these effects on their own. These are the yin and yang of T cellbased immune checkpoint treatment, Dr. Chan says. High TMB is less useful if a person is unable to present the mutations to the immune system. Having a high HED allows that to happen.

Our results help solve part of the mystery of why there is such a large variation in the effectiveness of immune checkpoint drugs.

Recent immunotherapy clinical trials have begun to include TMB in their evaluation of how effective checkpoint inhibitors are, Dr. Chan notes. But among different trials, there is great variation in the role that TMB plays. No one has been able to figure out whats going on, he says. It turns out, we should also be looking at HLA diversity. This finding may account for the unexplained variation thats seen in the role of TMB in immunotherapy trials.

He adds that it may also account for the different response rates that have been observed in different parts of the world. HED can vary dramatically depending on where someone lives.

The investigators are now working to develop a standardized way to report HED, so that it can be incorporated into future clinical studies. Dr. Chans team is in the process of evaluating HED with industry partners using global phase III trial data. They hope that this measure can eventually become a regular part of cancer diagnosis and be used to match people with cancer with the most personalized treatments.

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Genetic Variations Help Explain Why Immunotherapy Works Differently in Different People - On Cancer - Memorial Sloan Kettering

Somewhere along the road from sickness to health, the American medical system took a wrong turna big one.

The cost of care in our country is sky-high, yet our population health outcomes tend to be worse than those of other developed countries (many of which have universal health care). Major surgeries, treatments for long-term illnesses like cancer, and medical attention for catastrophic injuries are so expensive that people can lose their homes or be forced to declare bankruptcy. Even a routine visit to a general practitioner can cost hundreds of dollars. Yet Americans have some of the highest rates of heart disease, diabetes, and obesity in the world.

How did we get here?

In a talk at Singularity Universitys Exponential Medicine summit this week in San Diego, Dr. Jordan Shlain shared his thoughts on that question, as well as a framework for moving American healthcare forward. The first step, he believes, is a new Hippocratic oath, one thats been updated for our high-tech age.

It was the fifth century BC when Hippocrates put forth the idea that physicians should try to help people and do no harm (a pretty intuitive concept, one would think), among other ethical standards. The Hippocratic oath was born, and over time its been modified to reflect shifts in medicine and society. But the field of medicine has changed even more than the oath has, and Shlain believes its time for another overhaul.

He pointed to the beginning of early modern medicine as pivotal to the field. As new technologies came along that had potential to treat people more effectively, everyone wanted access to those technologies, so someone had to start manufacturing themand the incentive to do so was a profit.

When X-rays and penicillin were invented, we could see things wed never seen before and treat things wed never been able to treat before, Shlain said. Someone had to make X-ray machines and someone had to form a pharmaceutical company. But the convergence of medicine and business fed mounting costs, conflicts of interest, bureaucracy, and a focus on profits over patients.

Medical technology companies and pharmaceutical companies are now massive and complex, as are the medical and regulatory systems. Theres a lot standing between physicians and patients, Shlain said. It leads us to reactive medicine, and theres physician burnout.

The root of this problem, he believes, is that a corporate oath has superseded the Hippocratic oath in healthcare. The corporate oath says to increase shareholder value, generate profits, and constantly grow margins. But they dont know the outcomes on the other side, Shlain said. Exhibit A? The opioid crisis.

Since 1970, the costs of medications and medical devices have only gone upand so have corporate revenues. went up, cost of devices went up. But despite spending all this money and having all this expensive technology and medications, were not doing too well, Shlain said, pointing to a graph that shows life expectancy in the US falling since 2014. We need to differentiate between consumers and patients.

Shlains new oath consists of nine different statements.

1. I shall endeavor to understand what matters to the patient and actively engage them in shared decision making. I do not own the patient, nor their data. I am a trusted custodian.

Shlain pointed out that rather than asking patients What matters to you? physicians ask, Whats the matter with you? But to get the right answer, it should be a combination, and not just between doctors and patients, but in every interaction in the healthcare system.

2. I shall focus on good patient care and experience to make my profits. If I cant do well by doing good and prove it, I dont belong in the field of the healing arts.

We need to have some version of transparency for our outcomes, Shlain said.

3. I shall be transparent and interoperable. I shall allow my outcomes to be peer-reviewed.

Silicon Valley has gotten better at embracing a culture of learning from failure and even encouraging failure as a path to eventual advancement, but the medical field hasnt done the sameand perhaps rightfully so, since failure can mean a life lost. However, Shlain added, a byproduct of failure is almost always some sort of lesson.

4. I shall enable my patients the opportunity to opt in and opt out of all data sharing with non-essential medical providers at every instance.

Data privacy should be respected both as a path to trust and as a basic patient right.

5. I shall endeavor to change the language I use to make healthcare more understandable; less Latin, less paternal language; I shall cease using acronyms.

I would rename type two diabetes the over-consumption of processed food disease, because thats what it is, Shlain said. You dont get it, you participate in its process. But you didnt know it, because the language obfuscates that. So we really need to dig into language here, because language does tie to the metaphors we live by.

6. I shall make all decisions as though the patient was in the room with me and I had to justify my decision to them.

7. I shall make technology, including artificial intelligence algorithms that assist clinicians in medical decision making, peer-reviewable.

Everyone has proprietary technology and were supposed to use it despite not knowing how it works, Shlain said. Its in the interest of both practitioners and patients for this to change.

8. I believe that health is affected by social determinants. I shall incorporate them into my strategy.

Someones zip code can tell you more about their health than their genetic code, Shlain said. We need to focus on community.

9. I shall deputize everyone in my organization to surface any violations of this oath without penalty. I shall use open-source artificial intelligence as the transparency tool to monitor this oath.

Shlain pointed out that feedback loops in big corporations often arent productive, because people worry about losing their jobs. We need to create some mechanism of a feedback loop to ensure that this happens, he said.

This new oath isnt just for clinicians, Shlain emphasized. Its for everyone who touches the healthcare system in any way. That includes pharmaceutical companies, device manufacturers, medical suppliers, hospitals, and so on.

Given how fast new technologies are changing the healthcare landscape, we may need a totally new oath in ten years; what happens when robots are performing surgery, AI systems have taken over diagnosis, and gene editing can cure almost any congenital disease? Well need to continuously stay aware of how doctors roles are evolving, and update the ethical codes they practice by accordingly.

What we need is a culture of care, at every level, Shlain said. In order to change our paradigm, we need to have a set of principles that get us there.

Image Credit: Wikimedia Commons

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Why Medicine Needs a New Hippocratic Oathand What It Should Be - Singularity Hub

Conceptualised by Optimal Media Solutions, a division of the Times Group, Times Health Excellence 2019, is a platform to celebrate and honour outstanding achievements in Indian medicine. Optimal Media Solutions has over the years emerged as an integrated media solutions partner; going beyond conventional advertising, to provide customized and innovative options to clients.

The 2nd edition of this milestone event culminated in a glittering ceremony at Sheraton Grand Bangalore Hotel at Brigade Gateway, Yeshwantpur on 17th October 2019. The august gathering included the presence of distinguished guests and illustrious awardees from the field of medicine. Conceived as an innovative approach to document, disseminate and project new approaches that involve medical and health professionals, the event was envisioned to provide a boost to the way success stories are preserved and shared. As a part of this initiative, the pioneering contributions of some eminent medical practitioners were presented and applauded. Several thought provoking and enlightening presentations were made by renowned doctors, who are eminent practicing professionals.

The proceedings began with a brilliant presentation by Dr. Meenakshi Bhat, Professor & Mazumdar-Shaw Research Chair in Clinical Genetics, Centre for Human Genetics Bangalore. Her presentation titled Rare Genetic Disorders: Every Life Matters was an eye-opener on medical conditions that are largely ignored, but can be identified through medical advancements.

Dr. N K Venkataramana, Founder Chairman & Chief Neurosurgeon BRAINS, followed with an engaging presentation on Frontiers in Neurosciences. He spoke about the various developments in the field with regard to cutting edge services in prevention, awareness, advocacy, acute and chronic care, regeneration, rehabilitation, research and training.

Dr. Ann Agnes Mathew, Paediatric Neuromuscular Specialist, Sagar Hospitals Bangalore, then made a presentation on Inherited Muscle and Nerve diseases: Can India lead the world? that outlined the challenges faced in the industry.

Dr. Sandeep Nayak, Director of Surgical Oncology, MACS Clinic & Fortis Hospitals, Bangalore, made a presentation on the topic Revolutionising Cancer Care: Which Way Are We Heading? He spoke at length about several surgical innovations in oncology, which have changed the way the disease is tackled.

Dr. Mahendra S K, Senior Consultant Orthopaedic surgeon and Chairman, Matru Multispecialty Hospital, made a presentation on Orthopaedic surgeries, reviving quality of life...empathy above techniques. His inspiring speech highlighted several case studies, where those who suffering chronic conditions that had been given up on, were treated successfully with appropriate interventions.

Celebrity guest, Ms. Swara Bhasker, a popular Bollywood actress was also in attendance at the event. She added a touch of glamour with her gracious presence.

Those who were applauded at Times Health Excellence 2019, were trailblazers who have pushed all possible boundaries, and nurtured a passion for innovation, continuously seeking out ways to make things better for the holistic development of our nation. Their skill, talent, discipline has paved the way for many game changing initiatives and helped fuel their growth and strengthen Indias position in healthcare.

Our Sponsors: Premium Township Partner Karle Town Centre, Festive Gifting Partner LAL,Refreshed By Heineken 0.0

Disclaimer: Content Produced by Times Health Excellence

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TIMES HEALTH EXCELLENCE 2019 - HONOURING OUTSTANDING CONTRIBUTIONS IN MEDICINE - Times of India

Researchers have identified complement genes that appear to play a role in vision loss associated with multiple sclerosis (MS), and this finding could help researchers monitor and predict the progression and severity of MS, according to a study published in Brain.

Even though previous studies have identified gene variants associated with the risk of developing MS, until now, there have been no identified gene variants associated with MS severity.

Multiple sclerosis is a heterogeneous disease with an unpredictable course and a wide range of severity; some individuals rapidly progress to a disabled state whereas others experience only mild symptoms, the authors explained.

In 374 patients with all types of MS, the researchers used an imaging technique that allows them to assess damage to the nerve cells in the retina. Patients underwent an average of 4.6 scans between 2010 and 2017, and the authors reported that the rate of deterioration was a loss of 0.32 micrometers of tissue per year per patient, on average.

After they identified the patients who had the fastest deterioration rates, the researchers collected DNA through blood samples to identify genetic mutations. They identified 23 DNA variations that mapped to the complement gene C3.

Once they identified the variants, they analyzed DNA from blood samples of 835 patients with MS in an existing clinical trial who underwent periodic vision testing. The researchers noted genetic changes in the complement genes C1QA and CR1 in patients whose ability declined the fastest in the vision tests. Patients with mutations in C1QA were 71% more likely to develop difficulty with the vision test and patients with changes in CR1 were 40% more likely.

The authors plan to repeat the studies in larger populations and conduct animal studies investigating the function of complement proteins to better understand the mechanism behind their ability to kill nerve cells in patients with MS.

"Although we have treatments for the type of MS where symptoms come on in burstscalled relapsing-remitting MSwe don't have any way to stop the kind of MS in which the nerve cells start to die, known as progressive MS," Peter Calabresi, MD, professor of neurology and neuroscience at the Johns Hopkins University School of Medicine and codirector of the Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, said in a statement. "We believe that our study opens up a new line of investigation targeting complement genes as a potential way to treat disease progression and nerve cell death."

Reference

Fitzgerald KC, Kim K, Matthew D Smith, Aston SA, et al. Early complement genes are associated with visual system degeneration in multiple sclerosis. Brain, 2019; 142(9):2722. doi: 10.1093/brain/awz188.

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Researchers Identify Genes With Potential to Predict Progression and Severity of MS - AJMC.com Managed Markets Network

PTC Therapeutics announced a strategic partnership with Aldevronto ensure the production of high-quality plasmid DNA to be used with PTCs investigational gene therapies, including AGIL-AS for the treatment of Angelman syndrome (AS).

PTCs growing gene therapy pipeline for genetic disorders of the central nervous system (CNS) also includes an investigational gene therapy for AADC deficiencythats nearing submission to the U.S. Food and Drug Administration (FDA), as well as candidates for Friedreichs ataxiaand Angelman syndrome that are at earlier development stages. Other candidates for cognitive disorders and inherited retinal disorders are in preclinical research.

Our strategic collaboration with Aldevron represents our continued commitment to produce and provide the highest quality product to patients, Neil Almstead, PhD, PTCs chief technical operations officer, said in a press release.

Our gene therapy pipeline is addressing the unmet needs of multiple patient populations, and we feel an urgent need to develop safe products with the utmost speed. The development of relationships with top-tier companies like Aldevron aligns with our goal of partnering with the best collaborators as we drive meaningful improvements in the lives of patients, Almstead said.

PTCs gene therapy candidate for Angelmans syndrome is called AGIL-AS. It uses a modified virus that does not cause infection called an adeno-associated virus (AAV) to deliver a working copy of the UBE3Agene, the faulty gene in Angelman syndrome, to the brain and spinal cord of patients. The process is designed to restore production of the E6-AP protein produced by the UBE3A gene, this way improving cell function and rescuing neurological defects in Angelman syndrome.

Preclinical studieshave shown that AGIL-AS targets nerve cells in the brain, increases levels of E6-AP, and eases AS-like cognitive deficits in animal models of the disease.

AGIL-AS was granted orphan drug designationfrom the U.S. Food and Drug Administration in 2015, followed by a similar designation from theEuropean Commission in 2016.

Under the agreement, Aldevron will manufacture the plasmid DNA (circular molecules of DNA) where the functional version of UBE3A gene will be enclosed for delivery. The company ensures the materials are produced under Good Manufacturing Practice (GMP), a set of guidelines allowing products to be consistently made and controlled according to quality standards.

It is truly an honor to work with PTCs motivated team of experts. They are making enormous contributions to the future of genetic medicine, saidMichael Chambers, founder and CEO of Aldevron.

This is Aldevrons mission to serve scientists and researchers who are relentlessly pursuing cures for people who need them, he added.

Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.

Total Posts: 11

Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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PTC, Aldevron Partner to Advance Angelman and Other Gene Therapy Candidates - Angelman Syndrome News

Call it The Case of the Dueling Genes. A woman at high risk for early-onset Alzheimers disease because of an inherited genetic mutation unexpectedly stayed dementia-free for decades, and investigators believe a different genetic mutation may have protected herproviding potential clues for an Alzheimers treatment.

The womans family carries a genetic mutation known to cause early-onset Alzheimers. However, she did not develop signs of the disease until her 70s, nearly 30 years after the expected onset. Researchers suspect she may have been protected because she also had two copies of the APOE3 Christchurch (APOE3ch) gene variant. Findings of a case study published in Nature Medicine suggest that two copies of the APOE3ch variant may protect against Alzheimers.

Early-onset Alzheimers is rare, representing less than 10% of all people who have the disease. Risk for both early- and late-onset Alzheimers disease is affected by genetic factors.

For the study, investigators at Massachusetts General Hospital, in collaboration with other researchers from Colombia, Boston, and Phoenix, looked at genetic data from a Colombian family with more than 6,000 living members. Family members who carry a rare gene mutation called Presenilin 1 (PSEN1) E280A have a 99.9% risk of developing early-onset Alzheimers disease.

This woman carried the PSEN1 E280A mutation. However, she also had two copies of the APOE3ch gene variant, unlike any other affected relative. Imaging tests showed that she had large amounts of amyloid protein deposits, a hallmark of Alzheimers disease, in her brain. But the amount of tau tangles, another hallmark of the diseaseand the one more correlated with how thinking and memory are affectedwas relatively low.

Experiments as part of the study showed that the APOE3ch variant may reduce the ability of APOE to bind to certain sugars called heparan sulphate proteoglycans (HSPG). APOE binding to HSPG has been implicated as one mechanism that may contribute to the amyloid and tau protein deposits that destroy the brain. The research suggests that a drug or gene therapy that could reduce APOE and HSPG binding has the potential to be a new way to treat or prevent Alzheimers disease.

The study was funded in part by the National Institute on Aging.

Source: NIH, November 4, 2019

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Her Genes Cause Early Alzheimer'sSo How Did She Avoid It? - Managed Care magazine

These Five Life Science Organizations are Striving to Cure HIV

For those that lived through the devastation and horror of the HIV/AIDS epidemic of the early 1980s, effective treatment, let alone a cure for Human Immunodeficiency Virus (HIV), seemed unimaginable.

Some three decades later, a host of Maryland life science companies and research organizations are getting closer to making what was once unthinkable, real.

So little was known about this devastating immune disorder in the early phases of the HIV/AIDS epidemic.

In the early days of the HIV/AIDS crisis, the BioHealth Capital Region was the epicenter of HIV/AIDS research, with much of this groundbreaking research occurring within the lab of the now famed NIH researcher, Dr. Robert Gallo. In 1983 and 1984 Gallo and his collaborators co-discovered and confirmed that the virus responsible for the killer disease known as AIDS was human T lymphotropic virus type III (HTLV-III). Gallo and the company went on to develop the first test that identified the virus in humansthe HIV-antibody blood test.

By 1983 the disease had started to spread globally. By 1999, approximately 33 million people across the globe were living with HIV and an estimated 14,000,000 million people had died from AIDS since the epidemic began.

The 1995 approval of Highly Active Antiretroviral Treatment (HAART), which was the result of the remarkable, collaborative efforts of the scientific community, led to the reduction of AIDS-related deaths and hospitalizations by 60-80%. A short time later what was once a three-drug cocktail had been transformed into a pill taken once daily by HIV sufferers.

As of 2017, 19.5 million people are estimated to be receiving antiretroviral treatment globally. While one of the greatest achievements in medical history, HAART and subsequent treatment forms do not cure HIV. Within just weeks of stopping treatment, the virus returns to full strength and chronic inflammation caused by suppressed HIV can lead to adverse health effects over the long term. Current HIV treatments control it but do not cure it; in fact, research shows that those being treated for HIV are more susceptible to other diseases and health risks at an earlier age.

Despite the amazing advancements in HIV/AIDS treatments, HIV/AIDS continues to be a major global health threat.

It would be a fitting conclusion for an HIV cure to emerge from the state where the virus was first linked to AIDS and where the first human diagnostic was developed.

Multiple Maryland companies and research institutions are on the leading-age of HIV research and development, making the state a hotbed of potential next-generation HIV therapies and, possibly, the source of a cure for this devastating global health issue. Some of the most promising cure candidates are coming out of Marylands thriving cell and gene therapy cluster.

Lets take a look at some of the amazing progress thats happening right now across Maryland and take a deeper dive into five of the leading organizations that are on a mission to develop the first HIV cure.

AGT is a gene and cell therapy company with a proprietary gene-delivery platform to rapidly develop gene and cell therapies to cure infectious diseases, cancers and monogenic disorders.

One of its lead gene therapy products is a potential functional cure for HIV. AGT just announced that it has submitted the IND to the FDA for a Phase I trial of its autologous cell therapy for HIV.

While HIV has become a manageable chronic virus for many, in less developed countries HIV/AIDS is still a devastating illness. Developing an HIV cure would relieve millions from the side effects of antiretrovirals used to suppress HIV and prevent AIDS, avoid the serious quality-of-life issues of long-term treatment, and potentially save the lives of countless others.

AGT is currently developing a highly innovative HIV treatment strategy that uses the tools of genetic medicine for immunotherapy to potentially create a functional cure for HIV.

If we are successful, patients will be able to throw away their medication, will not progress to AIDS, and will be immune to future HIV exposures.

The potential single-dose treatment would be delivered as a genetically-modified cell product made from a patients own cells. AGTs strategy is unique because it focuses on the key immune cells responsible for catalyzing strong immunity against a virus. AGTs treatment strategy seeks to protect these cells; one of the first cell subsets to be disabled by HIV. This subset of cells is understood to be critical to building an immune response to any virus. If achieved, the cells natural process of immunity is restored and any future rise of HIV in the body will be attacked by an individuals own immune system.

AGTs treatment includes the production of an autologous cell product that is highly enriched for HIV-specific CD4+ T cells that are then transduced with a lentivirus vector known as AGT103 to protect against HIV-mediated T cell depletion. The combination of these enriched cells and the lentiviral vector forms a cell product AGT has dubbed AGT103-T. This cell product is delivered intravenously to HIV patients. AGT103-T should control viremia and work to remove infected cells from the body, thus eliminating the need for lifelong antiretroviral treatment.

AGT is currently collaborating with the Institute of Human Virology, University of Maryland Baltimore to collect leukapheresis specimens from HIV positive individuals for an ongoing observational study performing and qualifying the cell process, which is explained in greater detail here. The company expects its potential HIV cure to move into clinical trials in the next six months.

IHV is part of the University of Maryland School of Medicine and is a recognized leader in the virology field. IHV was founded by Dr. Robert C. Gallo who co-discovered HIV and developed the first HIV blood test.

IHV is heavily focused on HIV/AIDS research and the organization is currently progressing a promising HIV/AIDS vaccine through its pipeline. IHV01 (FLSC-001) has completed a Phase I trial and was supported, in part, from funding provided by the Bill and Melinda Gates Foundation.

This potential HIV/AIDS treatment seeks to neutralize the different strains of HIV found across the globe from the moment of infection. IHVs HIV/AIDS research is focused on the CCR5 chemokine receptor that plays a crucial role in HIV-1 infection and as such offers an important potential therapeutic target. (IHV Website). IHV is striving to develop biological HIV/AIDS treatments that are less expensive, have fewer adverse impacts and are more accessible to patients around the globe.

Lentigen is a leading provider of custom lentiviral vectors used in cell and gene therapy research and development. For HIV, Lentigen is at the forefront of efforts to use Chimeric Antigen Receptors (CAR) T-Cell therapy to improve the treatment of HIV and possibly cure it.

Lentigen, along with researchers at the University of Pittsburgh in Pennsylvania and the Albert Einstein School of Medicine, has been conducting a promising study of the use of CAR T in the treatment of HIV. The researchers developed duoCAR T cells that were able to kill white blood cells infected with a range of HIV variants. Testing in mice also produced promising results. Mice with humanized immune systems were simultaneously injected with CAR T cell and HIV-infected human cells into their spleens. When the spleens were examined a week later, five of the six mice had no identifiable HIV DNA and their viral levels had decreased by 97.5% (source: Science).

The study hopes to test the duoCAR T approach in HIV-infected people in the near future.

IBBR is a joint research enterprise of the University of Maryland, College Park and the National Institute of Standards and Technology (NIST). Last year IBBR received $3.9M from the National Institutes of Health (NIH) to develop a multi-specific, single-agent antibody therapeutic against HIV-1 to block virus infection and to clear the reservoir of HIV-infected cells from the body, according to an IBBR press release from November 2018.

The project is led by Dr. Yuxing Li, Associate Professor, Department of Microbiology and Immunology, University of Maryland School of Medicine, and Fellow at the Institute for Bioscience and Biotechnology Research (IBBR), in collaboration with Dr. Qingsheng Li, University of Nebraska-Lincoln, and Dr. Keith Reeves, Harvard Medical School/Beth Israel Deaconess Medical Center.

IBBRs research has focused on overcoming some of the limitations of existing antiretroviral (ARV) HIV treatments, including adverse side effects, ARV treatment drug resistance and how HIV integrates into the human genome, creating pockets of HIV that ARV cannot eliminate. Dr. Li and his group have produced bi and tri-specific antibodies that demonstrated neutralization of 95% of circulating HIV-1 viruses. These bi and tri-specific antibodies can also bind to multiple locations on the HIV-1 surface glycoprotein Env, which could potentially thwart treatment resistance via mutation. The team is now working to optimize their multivalent antibody constructs to recognize Env proteins on the surface of latently infected host cells, and to signal other immune system components to destroy those cells that contain the hard-to-reach viral pockets, or as the team calls them, a viral reservoir. (IBBR press release)

NIAID has been at the forefront of HIV research for decades and continues to be a major player in the research and development of possible HIV treatments and potential cures. NIAIDs research into HIV played a critical role in developing ARV drugs that transformed HIV into a chronic condition rather than a fatal infection.

NIAID-supported research has led to many ARV drug improvements, including reducing the number of pills required, diminishing adverse impacts and identifying the best drug combinations. The organization works with many leading global HIV/AIDS research organizations to identify and develop better HIV treatments.

NIAID is focused on both developing new HIV treatments as well as supporting other researchers and research organizations investigating new therapies. The ultimate goal is to potentially make HIV treatment a single dose, lifetime treatment, and, eventually, the complete eradication of HIV. NIAID is involved in many research and development projects focused on HIV and there are too many to dig into in a single article. Some of their current HIV research and development efforts are focused on investigational long-acting HIV drugs, rilpivirine LA and cabotegravir LA, for patients that have had difficulty following conventional antiretroviral therapy programs. Another NIAID study will test combining monthly injections of cabotegravir LA and infusions of an NIAID-discovered broadly neutralizing antibody called VRC01LS to see if the combination can keep HIV suppressed in people whose infection was previously controlled by antiretroviral therapy.

The organizations support has also helped in the discovery of the experimental drug islatravir (also known as EFdA or MK-8591) and maturation inhibitors. NIAID also has partnered with the Maryland industry, including a research collaboration agreement with AGT for research studies on the companys cell and gene therapy for HIV/AIDS.

A partnership between NIAID, Frederick National Labs for Cancer Research (operated by Leidos Biomedical Research, Inc.) and a team of collaborators recently developed 38 new simian/human immunodeficiency viruses (SHIVs) for prevention and treatment studies. These new SHIVs have closed a gap that previously existed in HIV research. These SHIVs are pathogens engineered in the lab that can help in the investigation of potential new HIV therapies as well as other treatments and vaccines.

These SHIVs target HIV subtype C, which causes approximately half of all HIV infections, and were created using HIV samples from people recently infected, allowing better modeling of more current forms of HIV subtype C circulating globally. The stronger modeling will increase pre-clinical researchs ability to predict effectiveness. Other SHIVs had used samples acquired from patients that had been infected long before the sample was pulled, limiting the SHIVs effectiveness against more current strains of HIV. While improvements are still needed, including challenges with replication, these new tools for HIV research and discovery hold tremendous promise.

In the late 1970s and early 1980s finding a cure for HIV/AIDS wasnt even on the radar. The scientific community was racing to understand the fundamentals of a virus that was rapidly spreading devastation and death across the globe. The speed with which the medical community came to understand the disease and to develop treatments like HAART is one of the truly amazing stories of the 20th century.

One or several of these Maryland companies and research institutions have a real chance to achieve what was once unthinkablefinding a cure for HIV that could help tens of millions of people across the globe live better, healthier and longer lives.

If an HIV cure emerges from Maryland, the BHCR community will have helped write the final chapter of HIV/AIDS terrible yet hopeful story.

Steve has over 20 years experience in copywriting, developing brand messaging and creating marketing strategies across a wide range of industries, including the biopharmaceutical, senior living, commercial real estate, IT and renewable energy sectors, among others. He is currently the Principal/Owner of StoryCore, a Frederick, Maryland-based content creation and execution consultancy focused on telling the unique stories of Maryland organizations.

Link:
Heres Why the First Cure for HIV Could Emerge from Maryland - BioBuzz

A woman in Colombia was destined to develop Alzheimers disease in middle age due to a genetic mutation. But she never did. In fact, she made it into her 70s showing no signs of dementia.

A few years back, the woman partook in a study at the University of Antioquia in Colombia that looked at 6,000 people that she was distantly related to. About a fifth of these participants, including the woman in question, had a genetic predisposition to Alzheimers. She carried a mutation in the gene responsible for a protein called presenilin 1, giving her a greater than 99 percent risk of developing dementia and cognitive issues in her 40s or 50s. But she remained in good cognitive health.

To satisfy the curiosity of baffled scientists, she headed to Boston in 2016 to have her brain, blood, and genome examined. Scans of her brain revealed high levels of amyloid protein, a hallmark of Alzheimers disease. However, she was symptom-free, suggesting something mysterious was protecting her from its effects.

Next, the researchers sequenced her genome, finding that she had a very rare mutation of a gene called APOE. This gene has previously been implicated in Alzheimers one variation can increase risk, another can decrease it, while the most common type has no effect. However, the woman had two copies of another variant, known as Christchurch, which was discovered in 1987 in Christchurch, New Zealand. The findings are reported in Nature Medicine.

The researchers think that the Christchurch mutation might prevent the APOE protein from binding with certain sugars, a process implicated in the build-up of amyloid proteins and tau proteins, another Alzheimers hallmark, in the brain. Therefore, a drug that inhibits this process could stave off the disease, although such a drug likely would not be available soon.

Early-onset Alzheimers affects a small minority of people and only about 5 percent of Alzheimers patients are diagnosed with it. The condition can have substantial impacts on a persons life as it tends to develop during your 40s or 50s, decades before Alzheimers symptoms usually start to set in. Alzheimers is a progressive disease, meaning that symptoms like memory loss, confusion, and delusions get worse over time. Theres currently no cure, so gaining a better understanding of what causes the condition is key.

Sometimes close analysis of a single case can lead to a discovery that could have broad implications for the field, said National Institute of Aging Director Richard J. Hodes in a statement. We are encouraged that as part of our wide array of studies, this research in the unique genetic makeup of an exceptional individual can reveal helpful information.

Read more here:
Colombian Woman In Her 70s Immune' To Alzheimer's Thanks To Rare Genetic Mutation - IFLScience

Dashing through the snow at 25 miles an hour,Heather Huson97 got her first thrill as a musher at age 7. From then on, she was hooked on dog sledding, and raced competitively for almost 30 years throughout North America.

By the end of her racing days, she had competed twice in sled dog racings equivalent to the Olympics the International Federation of Sleddog Sports World Championships. And she ended her racing career with a bang, winning an extremely competitive six-dog class race at the 2004 Tok Race of Champions in Tok, Alaska.

Heather Huson shares time with a sled dog at the Baker Institute.

Now an assistant professor of animal science, Huson is co-leader of a $4.2 million project studying close to 100 Alaskan sled dogs between the ages of 8 and 13, former athletes past their glory days. The study, which began in 2018, is a quest for one of the holy grails of medicine: how to slow aging.

This project allows me to work with sled dogs again, but now Im studying their aging and health, said Huson, a molecular geneticist in the College of Agriculture and Life Sciences.

Huson and co-leaderDr. John Loftus, assistant professor of small animal medicine in the College of Veterinary Medicine, are trying todetermine whether a drug that inhibits an enzyme called reverse transcriptase can mitigate aging and extend life in older dogs. Private donations fund the project through the Vaika Foundation, a nonprofit group of scientists and veterinarianson a mission to extend the health and life span of domestic animals.

The project will serve as a proof of principle for whether reverse transcriptase inhibitors could be an elixir. If confirmed, new finely tuned drugs could be developed for both dogs and humans.

While we love dogs, and we care about extending the life span of dogs for its own right, this is also a really good model for people, hopefully, in the future, Loftus said.

Genetics of aging

Other researchers, including project collaborators at the Roswell Park Comprehensive Cancer Center in Buffalo, New York, have found evidence in mice that reverse transcriptase inhibitors suppress tumors and extend life span.

The next step was to go to a model organism thats more closely related to humans in similar environments, and more similar to the types of diseases that people get, Huson said.

While we love dogs, and we care about extending the life span of dogs for its own right, this is also a really good model for people, hopefully, in the future.

John Loftus

In mammals, viruses that infected distant ancestors left behind some of their DNA, which are called genetic elements.

As we age, were finding these normally dormant DNA elements get turned on and then behave like viruses in the body, said Loftus, a veterinarian and researcherwho leads the immune system analysis on this project.When DNA elements get turned on, they can encode [for] a number of proteins, and reverse transcriptase is one of them.

In turn, reverse transcriptase plays a role in duplicating more of these genetic elements, which become randomly inserted in the genome and can lead to mutations and cancer.

And since these elements act like viruses in cells, they also trigger an immune response, which creates inflammation.

The federally approved drug being tested in the sled dog project is commonly prescribed to people for viral infections.

Our approach is going to be to give the dogs a reverse transcriptase inhibitor to turn the transcriptase off, Loftus said, and hopefully reduce inflammation, reduce the incidence of cancer and other diseases related to mutations and DNA damage, and ideally increase life span.

Heather Huson watches as a sled dog runs during play time in a fenced field at the Baker Institute for Animal Research at Cornell.

Why Alaskan sled dogs?

Dogs offer many advantages over mice as research subjects. They share with humans similar lifestyles and aging-related diseases like cancer and cognitive dysfunction, and serve as a model for studying Alzheimers disease.

Originally, the researchers proposed to study pet dogs. But maintaining a uniform diet for all participants and trusting owners to administer the drug consistently proved too unreliable.

We had the idea instead to create a colony of dogs we had control over, Huson said. They realized athletic dogs were housed in groups, in kennels, and as they age, owners kept their best dogs and often sold the rest to hobbyists or as pets.

So that gave us an avenue for how we could get these dogs, Huson said.

For her doctorate, Huson studied the genetics and selective breeding in Alaskan sled dogs at the University of Alaska, Fairbanks. She discovered that sled dogs are a genetically distinct breed. They have undergone intense selection for such traits as athleticism, but at the same time are subject to an open breeding scheme,with a diverse gene pool that makes for fewer genetic issues and diseases than pure breeds.

John Loftus greets a sled dog at the Baker Institute for Animal Research.

Yet they create a unique population that is still homogenous that we can study and say, this response to the drug is potentially related to the drug and not because its a poodle versus a beagle, Huson said.

In late May 2018, Huson and Loftus began acquiring dogs, which they kenneled at the Baker Institute for Animal Research at Cornell. Huson traveled twice to Alaska, and she and others, including students, picked up dogs from Canada, Michigan, Minnesota, Oregon, Washington and other states.

Locating dogs and bringing them to the Baker Institute required countless cross-country trips on planes and by vehicle. By September 2018, they had 102 dogs for the study. In March 2019, the researchers collected the firstbaseline data.

Testing aging over time

To test the drugs effectiveness, Huson and Loftus have been quantifying aging in the dogs every six months through three avenues immune function, behavior and physical condition. All the tests are noninvasive or minimally invasive.

They are testing two types of immune responses: adaptive responses that react quickly to infections; and innate responses where the immune system recognizes and delivers specific antibodies to fight a pathogen that previously entered the body. They are also checking blood for increases in markers for inflammation.

Four cognitive dysfunction behavioral tests involve an empty behavioral testing room with a video camera to record lone dogs as they encounter such things as a stranger sitting still in a chair, a familiar or novel toy, or a mirror.

Heather Huson racing in an Alaska Dog Mushers Association Challenge Series race in 2005 at the Jeff Studdard Sled Dog Race Track in Fairbanks, Alaska.

For physical tests, dogs are fitted with a racing harness and are trained to run on a treadmill with heart rate and electrocardiogram monitors. The treadmill has special sensors under the belt to record the pressure of each footfall, to detect limping that could come with arthritis. Another test times dogs as they pull one-and-a-half times their weight a distance of 40 yards using a pull harness.

It will take years to gather enough data for the researchers to make a definitive statement about the drugs effects. But funds have already been allotted to provide the dogs with a high quality of life until they die of natural causes.

Twice a day the dogs go outside for play time. As soon as the kennel doors open, the dogs, tongues flapping, scurry excitedly down a long hallway toward the light of an open door that leads to three separate fenced fields where they play, run, sniff the grass and greet the student volunteers outside.

It reminds Huson of her childhood, when her family owned as many as 50 sled dogs.

I used to train dogs to run all the time, Huson said. Now were training them to run in a slightly different scenario. Its fun and rewarding. And, its therapy for us.

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Sled dogs lead the way in quest to slow aging - Cornell Chronicle