Category Archives: Genetic Medicine

One night in her Nashville apartment, Bre Banks read a comment from her boyfriend on Facebook. They were in a shaky spell, and his words seemed proof she would lose him. She put her laptop down on the couch and headed to the bedroom to cry. My legs seized up, and I fell, she recalled. With her knees and forehead pressing into the carpet, she heard a voice that said, Slit your wrists, slit your wrists. She saw herself in the bathtub with the blood flowing. She was terrified that if she moved she would die.

Banks, then 25, was a disciplined graduate student with a job and close friends and had no psychiatric history. I had never considered suicide an option, she says. But for the next three days, she couldnt sleep while the voice and disturbing images persisted. After seeing a therapist, she decided to teach herself techniques from dialectical behavior therapy, one of the few treatments shown to reduce suicidality. The voices and images came back over the next few months, but eventually faded. Eight years later, Banks now evaluates suicide prevention programs across Tennessee as a manager at the large mental health provider Centerstones research institute, and she and the same boyfriend just celebrated their 10th anniversary.

In the public imagination, suicide is often understood as the end of a torturous decline caused by depression or another mental illness. But clinicians and researchers know that suicidal crises frequently come on rapidly, escalating from impulse to action within a day, hours, or just minutes. Many also point to the fact that they may strike people like Banks, who are otherwise in good mental health.

That understanding is one reason a movement is building to define suicidality as a condition in its own right. Most recently, researchers from Mount Sinai Beth Israel and Florida State University have agreed to collaborate on a joint proposal for a new diagnosis in the next Diagnostic Statistical Manual of Mental Disorders (DSM), a handbook published by the American Psychiatric Association. The criteria include familiar symptoms of depression, but these symptoms occur in an acute state that is not currently obvious to clinicians. Proponents say it could spur more research and make it easier for suicidal patients to get the care they need.

Suicide rates have been rising sharply since 1999, figures from the Centers for Disease Control and Prevention (CDC) show. More than half of those who take their lives do not have a known mental health condition. There is also no established way to pinpoint when a patient is in immediate danger. You cannot rely on people telling you when they are or are not suicidal, said Igor Galynker, a professor of psychiatry at Icahn School of Medicine in New York.Some have expressed skepticism. Far too many diagnoses in psychiatry come and go, said George Makari, a Weill Cornell Medicine psychiatrist and historian of psychiatry. The idea that suicidality may not be a symptom of something else a mood or personality disorder is novel. If theyre making the claim that weve been seeing this upside down for a long time, he said, thats fascinating.

Research backs that up: A 2019meta-analysisof 71 studies conducted around the globe found that about 60 percent of people who died by suicide had denied having suicidal thoughts when asked by a psychiatrist or general practitioner. Here in the U.S., a2016 studyexamined data from four health systems that use standardized questionnaires in primary care and specialty clinics. (The questionnaires ask whether the patient has experienced thoughts that you would be better off dead or of hurting yourself in some way.) Although the answers did predict future suicide attempts to some extent, there were plenty of false negatives. Thirty-nine percent of the suicide attempts and 36 percent of the suicide deaths occurred among patients who had responded not at all to the key question. In another study, about a quarter of the suicide attempts were made by people who reported zero suicidal thoughts.

Its easy to assume they were lying, but thats not quite true. Greg Simon, a psychiatrist and investigator at Kaiser Permanente Washington in Seattle, who led the 2016 study, was involved in a follow-up study based on interviews with 26 people who had made attempts after denying any suicidal thoughts on the standard questionnaire. The interviews revealed that some people had lied, he said. But they also revealed people who had provided aspirational responses they weretryingnot to have suicidal thoughts and people who had experienced no suicidal thinking whatsoever. (Among the latter group, alcohol often factored into their attempts.) None of them woke up that morning with a plan to die that day.

For his part, Galynker determined long ago after he lost a patient who took him by surprise that he couldnt rely on patient reports. In 2007, he set out to develop a set of symptoms that would help pinpoint imminent suicide even if the patient didnt report suicidal thinking. We hypothesized that the pre-suicidal state leading to suicidal action was short-lived, kind of like pulling a gun trigger, he said. In 2009, he called it suicide trigger state. Over dozens of research papers, he explored various symptoms as predictors, developing checklists and then testing how well they predicted future behavior. While these checklists are still new, they are being used to screen for suicidal risk among high school students in Moscow, Russia, and among hospital patients in Chicago.

In 2017, Galynker coined the termsuicide crisis syndrome. People with this syndrome feel trapped, though they might not think of death per se. They may be flooded with misery and unable to think clearly. Certain thoughts, like Banks images and voices, return repeatedly, no matter how much they are resisted. They may experience mood swings or overwhelming emotional pain.

At Florida State University, Thomas Joiner, the author of several books on suicide and the editor of a suicide journal, outlined his own criteria for a quick-onset suicide crisis, which he calls acute suicidal affective disturbance. This describes rapidly escalating plans for suicide over hours or days faster than clinicians may expect. The key difference is that Joiner includes reports of suicidal thinking as an essential criterion.

The pair teamed up more than two years ago when the first paper describing both of their diagnoses appeared. Together, the two researchers envision a new DSM suicide diagnosis with two sub-types, one with thoughts of suicide, and one without. Before this diagnosis is approved for the DSM, however, the researchers may need to show more conclusively that the phenomenon they describe isnt a symptom of depression or another mental illness, and that their methods of screening for it are effective.

Psychiatrist Michael First at Columbia University, who presided over earlier revisions of the DSM, sees a suicide-specific diagnosis as an appealing idea. If the melding of Galynkers and Joiners formulations worked well and proved to be accurate, First said, then it would clearly be very useful to have it.

Clinicianscurrently struggle with little guidance on how to identify imminent risk or make sense of suicides that seem to come out of the blue.

Nearly once a week, attending psychiatrist Dmitriy Gekhman at Mount Sinai Beth Israel sees a patient who has attempted suicide and is hard to classify, though he must find a relevant code for each patients chart. You kind of go through the history and everything, and theyre not depressed. They dont meet the criteria for depression, they dont meet criteria for bipolar disorder, and they dont have a personality disorder, he said. We just discharged somebody this week who that happened to, and we still have somebody on the unit now.

If a diagnosis based on Galynkers and Joiners research were put in place, it would put the patients doctors on notice that the patient is a risk for suicide with rapid onset. Over time, its possible that clinicians and even teachers and parents would become better at seeing the signs. The diagnosis, Joiner explained, is a warning sign for the future.

Detroits Henry Ford Health System provides a glimpse of how suicide prevention might evolve. At Henry Ford, suicide is considered its own mental health category, not primarily a symptom of depression. In 2002, the health system began a series of initiatives, and reduced patient suicide rates a dramatic 80 percent over the next seven years.

The staff at Henry Ford discovered that from 2000 to 2010, only half of patients who died by suicide had received a mental health diagnosis, closely matching current national statistics. This could be undiagnosed illness, but I think a lot of people dont meet the criteria, said Brian Ahmedani, who directs the health systems Center for Health Policy & Health Services Research.

Henry Ford screens everyone with questionnaires asking about suicidal thoughts, a practice the Joint Commission, which certifies health care organizations, started recommending in 2016. But in its behavioral health units, the risk assessment focuses on triggers, such as a job loss. Ahmedani says that patients in the highest risk percentile usually have a number of triggers: chronic pain, opioid use, and insomnia, for example. Because assessing the many possible combinations can be difficult, Henry Ford uses artificial intelligence to analyze electronic medical records, helping clinicians who may not have time to catch a perfect storm before its already too late. Veterans are a high-risk group, so the Veterans Affairs (VA) has begun using these algorithms too.

Currently, suicidal people are often prescribed antidepressants. However, other than lithium, most often used to treat people with bipolar disorder, theres little evidence that medication prevents suicide, Ahmedani observed. New VA clinical guidelines alsosupportshort-term infusions of a drug calledketamine.

Henry Ford offers treatments specific to suicide: identifying triggers and coping mechanisms, for example. It also offers cognitive behavioral therapy and dialectical behavior therapy, the treatment that helped Banks. Patients are encouraged to develop a safety plan that includes removing guns or painkillers from the home, and an idea of who they might call under duress.

David Covington, a suicide prevention activist, said, we used to think that if you treat addiction, the mental health will get better, and the other side thought if you treat mental health, the addiction will get better. Now we say you have to treat both. Similarly, a person might need treatment for both suicide and depression.

The new diagnosis, more fundamentally, could change who we think might be driven to the extreme of a suicide attempt. Psychiatrists still refer to suicide attempts with a short buildup as impulsive, but Joiners team disputes that these are impulsive people. Megan Rogers, a Ph.D. candidate who works with Joiner, sees outpatients at the university clinic. She recalls one who within hours would go from no risk to high risk but had what she describes as a conscientious and vigilant, rather than impulsive, personality.

Still, some question whether a new diagnosis would actually benefit patients. For one thing, it isnt clear how such a diagnosis would influence treatment or whether it would save lives. There is simply no value in a prediction that cannot lead to an effective preventative measure, writes psychiatrist Matthew Large in a2018 paperevaluating suicide assessment approaches generally. More people could land in hospital psychiatric care, or be kept longer than they desire, he said. And while it is generally assumed that hospitalization can prevent suicide, this has never been demonstrated empirically. In fact, suicide rates are high among recently discharged patients and some say hospitalization can make things worse.

Galynker agrees that hospitalization is not necessarily the answer and is looking at new treatment methods. In the meantime, the diagnosis might communicate the higher risk to insurance companies, explained Lisa Cohen, a professor of psychiatry at Icahn School of Medicine and co-author with Galynker, giving patients better access to treatment options.

Psychiatrists who make decisions about hospitalization say they would appreciate more science to guide them. It would be incredibly helpful to have a very clear indication that someone is at higher risk, observed Julie Holland, who once presided over a psychiatric emergency room at Bellevue Hospital in New York. A close look at the buildup to a crisis would be invaluable. We do that when somebodys heart stops, or when somebodys heart is imminently stopping, said Chicago psychiatrist Leo Weinstein, who teaches at Northwestern University. Making the unstable state a diagnostic entity in its own right, like ventricular fibrillation or congestive heart failure, he says, is crucially important.

Temma Ehrenfeld is a writer and ghostwriter in New York drawn to philosophy and psychiatry. Her most recent book is Morgan: The Wizard of Kew Gardens. Follow her on Twitter @temmaehrenfeld

A version of this article was originally published on Undarks website as Can a New Diagnosis Help Prevent Suicide? and has been republished here with permission.

Continue reading here:
Treating 'suicidality' as its own medical condition could spur research, better treatment options - Genetic Literacy Project

A racial equity lending fund is tapping a new foundation for help funding its services.

Rende Progress Capital and the Michigan State University Federal Credit Union Desk Drawer Fund said Nov. 22 that they have formed a partnership to enhance RPCs business technical assistance and inclusive lending services within Kent County.

The services target excluded entrepreneurs seeking help to prepare them for small business loans in order to increase business ownership, eliminate the racial wealth gap and provide them alternatives to the barriers they face in some conventional lending.

The Desk Drawer Fund a new foundation of MSUFCU was established to support initiatives that promote its pillars of financial education and fostering entrepreneurship.

Eric Foster, RPC co-founder, chair and managing director, said the fund will enable RPC to continue its business technical assistance and pre-loan readiness sessions to help entrepreneurs improve areas of their business in preparation to obtain potential loans.

The partnership also includes support of RPCs activities and day-to-day operations.

I am excited that (MSUFCUs) values of community engagement and awards in diversity and inclusion connect with our unique mission to address the challenging issues of advancing economic equity for ethnically diverse entrepreneurs, Foster said.

This is RPCs first partnership with a credit union as a funding and organizational partner.

The partnership (between) Rende Progress Capital and the Desk Drawer Fund will help entrepreneurs identify opportunities and obtain resources to realize their dreams, said Whitney Anderson-Harrell, executive director of the Desk Drawer Fund and MSUFCUs chief community development officer.

Air share

The majority of flights between the Gerald R. Ford International Airport and Chicago now will be via a new 50-seat, two-cabin aircraft.

United Airlines newest fleet addition is the Bombardier CRJ-550, a regional jet that flies to 15 routes from Chicago, including to Grand Rapids. An additional 10 routes will come online in the coming months.

The plane is the same size as a 70-seat plane but contains only 50 seats, 10 being first class and the rest economy.

The aircraft features more legroom, storage and amenities than any other regional aircraft flying today, United said.

Theres space on the aircraft for every customer to bring a roller bag on board, eliminating the need to check bags. The plane also includes complimentary Wi-Fi.

Passengers riding in the first-class cabinet have access to a self-serve snacks and beverages center, similar to those offered in Uniteds international aircraft premium cabins.

Available only for the CRJ-550 for now, customers booking through united.com can view their seats before buying using the virtual seat map. The virtual seat map provides a walkthrough of the first-class refreshment center, suitcase cabinets and overhead bins.

Tree-mendous

Rockford Construction, the city of Grand Rapids and Grand Rapids Art Museum were on hand last week to bring holiday cheer to the heart of Grand Rapids in the form of a 41-foot concolor white fir tree.

The Christmas tree traveled more than 100 miles from Dutchman Tree Farmsin Manton to Rosa Parks Circle for installation.

The annual tradition takes months to plan and many partners to pull off without a hitch, and the time from delivery to tree lighting alone takes over a week. Decoration will take place in Rosa Parks Circle on Dec. 2, followed by the annual tree lighting from 5:30-7:30 p.m. Dec. 6.

"This collaborative project is a team effort taking months of strategy and planning, which many people don't realize," said Shane Napper, president at Rockford Construction. "This tree installation is a staple for the Grand Rapids community and just one of the many examples that make this city special. The tree installation the tree installation and decoration are one of the most exciting projects we get to work on each year and a great way for us to help make our community brighter for the holiday season."

Rockford Construction has been involved in the annual Christmas tree project for over 10 years.

Plans for the annual tree installation were included in long-term planning during construction of the Grand Rapids Art Museum. At the time, the teams developed an underground foundation hidden under the brick pavers in front of the museum. Year after year, installers remove pavers to unearth the secret foundation so that the tree can be placed safely and securely each year.

We are grateful for our community partners who help make this such a fun holiday tradition, Grand Rapids Office of Special Events Supervisor Evette Pittman said. We look forward to the tree delivery and decoration every year. Thanks to everyone involved in handling the logistics effortlessly and adding holiday cheer to the city we call home.

In addition to Rockford, the city and the museum, other partners on the installation include Buist Electric, Gelock Heavy Movers and Shine Decorators. The entire installation is handled on a volunteer and donation basis.

Strength in numbers

Pine Rest Christian Mental Health Services is participating in a National Institute of Mental Health study related to major depressive disorder. The study convenes investigators from around the world to carry out a genetic study of MDD treated with electroconvulsive therapy.

NIMH awarded more than $5 million to fund the Genetics of ECT study over five years. The National Network of Depression Centers, along with seven allied ECT centers in the U.S., has joined forces with the Psychiatric Genomics Consortium to conduct this study on a global scale. Pine Rest and Michigan State University are participating through their joint associate membership in the NNDC.

This study aims to collect genetic samples from 15,000 patients receiving ECT for severe depression across the U.S., plus an additional 10,000 patients from ECT centers around the world. The driving goal of the study is to identify genetic variation that 1) contributes to risk for severe MDD and indicates which patients may be good candidates for ECT, and 2) influences response to ECT and predict which patients may benefit from treatment.

This is a landmark study, said Peter Zandi, co-principal investigator, Johns Hopkins Bloomberg School of Public Health, representing not only the largest study of ECT ever conducted but one with potential to greatly improve how we understand cases of depression that are difficult to treat traditionally.

The hope is that comparing genetic profiles of patients who receive ECT with how well the treatment works for each patient will shed some light on how ECT works, who it works for and how to identify the best candidates for ECT treatment.

The co-principal investigators are Zandi, Dr. Patrick Sullivan of the University of North Carolina at Chapel Hill; Dr. Richard Weiner of Duke University School of Medicine; Dr. Daniel Maixner of the University of Michigan; and Dr. Irving Reti of Johns Hopkins Medicine.

The study began enrolling patients who will give a blood sample for genetic testing. Patients will answer some depression questionnaires with nursing staff before, during and after treatments, which is already done as part of current patient care.

Many studies are limited by small sample sizes, but with genetic studies, large sample sizes allow for better detection of trends or correlations, said Dr. Eric Achtyes, Pine Rests principal investigator for the study. Research like this, with many partners in a global network, allows the aggregation of data in a way individual institutions could not accomplish on their own.

Original post:
Street Talk: Opening their drawers | 2019-11-29 - grbj.com

Text Size:A- A+

Bengaluru: The Council of Scientific and Industrial Research (CSIR) has launched an ambitious project, IndiGen, to sequence whole genomes of diverse ethnic Indian population to develop public health technology applications.

The CSIR last month announced sequencing of 1,008 Indian genomes as part of the project. It aims to complete sequencing of at least 10,000 Indian genomes over the next three years.

A genome is an organisms complete set of DNA. It includes all genes, which house the DNA, and chromosomes. The genome contains all the data that is needed to describe the organism completely acting essentially as a blueprint. The genome can be understood through the process described as sequencing.

Whole-genome sequencing is the decoding of the entire DNA present in the human cell. This data can be analysed to understand the function of various genes, identify genetic mutations and explore how the mutations impact gene functions.

Genetic mutations underlie many diseases, including congenital conditions like thalassemia and diseases like cancer. Thus, deciphering a persons DNA can reveal information about that persons health.

This apart, analysing DNA data of human population can reveal population-level predispositions to diseases. Take the case of a specific Vysya community in Andhra Pradesh, which is believed to possess a genetic mutation that renders them susceptible to a category of anaesthetics.

Studying DNA data from patients who suffer a specific disease can also help trace the origin of that disease. The UK has been running a 100,000 programme creating a database of over 85,000 patients suffering from rare diseases/cancer to discover the mutations that underlie those diseases.

The UK is, however, not the only country investing in population genomics. The US, Japan, China, Australia, Saudi Arabia, Estonia, France, Dubai and Turkey have all embarked on genomic programmes to better understand the healthcare needs of their citizens.

The IndiGen project is Indias first step in collating such a national database for its citizens.

Also read: For the first time, India has a genome database. But are we ready to use it?

Around 70 million Indians suffer from rare genetic diseases. It is estimated that about 64 out of 1,000 live births in India carry a congenital birth defect. Yet the molecular basis of a number of diseases remains unknown.

Further, India has a unique genetic history underpinned by centuries of endogamy (marrying within the same community) practised in various communities.

The resultant South Asian genetic population is comprised of more than 5,000 genetic sub-groups. While diseases may appear rare in the entire Indian population, specific sub-groups may show a higher frequency of disease incidence.

Specific sub-groups, which practise endogamy, will also have a conserved mutation that has spread through that population as exemplified by the Vysya community case.

Another study had demonstrated some sub-groups containing a mutation that caused a predisposition to glaucoma.Thus, a comprehensive Indian genome project essentially will study disease prevalence within these individual ethnic populations.

The analysis of a significant sample set representative of a particular sub-population can provide data on the predisposition of various diseases present in that sub-group. Using this information, individuals belonging to that sub-group can make informed decisions to get screened for particular mutations. Those found to contain genetic mutations can make necessary lifestyle changes or seek medical assistance to lead healthier lives.

Some congenital diseases result when a child inherits two defective genes from a parent. For this category of diseases, pre-emptive action such as screening of partners before marriage or PGD (preimplantation genetic diagnosis) to pick healthy embryos can ensure the birth of healthy children.

Dor Yeshorim, a US-based not-for-profit organisation, runs a programme within specific Jewish communities to inform prospective couples of their genetic compatibility.

Over the past few years, this continued programme has led to the eradication of Tay-Sachs disease from at least one US-based Jewish community.

The analysis of genomic data, combined with medical information, from victims of rare diseases can reveal the mutations that underpin the disease. This data can be used to create improved diagnostics and therapeutics for targeting the disease. Newer tools like gene-editing can also be explored for treating genetic diseases.

Data assessments can massively impact healthcare in India either by helping couples raise healthy children or by creating avenues for better medical interventions for preventing or treating diseases.

The major challenge of a project of this scale is adequate and representative sampling of the population. The more the number of samples, the better the accuracy.

The genome projects of other countries target about 1,00,000 genomes. Indias target of 10,000 genomes in comparison is a good start but needs substantial expansion.

There also needs to be clarity on the sampling approach does the sample identify a representative set for each subpopulation or for each rare disease? An exercise of a massive scale as this has to be led by a specific predetermined objective.

The second challenge is of consent a publicly-funded project of this nature may likely start off as a research project based in academic labs, but the creation of diagnostic or therapeutic tools would be facilitated by sharing the data with commercial ventures.

While taking volunteer/patient samples, it is important to take consent for the use of any data in creating commercial products, may it be diagnostics or therapeutics. If commercially viable products are created based on contributed data, financial or benefit-sharing agreements need to be addressed beforehand to prevent any unnecessary litigation later on.

The database for this project not only contains genetic information, but also medical and sensitive personal information, and contributors should have a say in how much information gets shared with additional partners.

A third question that needs to be sorted is about how much information to share with the donors. Dor Yeshorim believes that burdening people with mutation information can lead them to unnecessarily make lifestyle changes. Thus, clinically actionable information should only be shared where robust scientific proof exists, linking the mutation to a disease.

To implement this, clinicians and genetic counsellors need to be trained to determine best medical intervention in the context of the particular patient. Hence, capacity building to gather, analyse, interpret and communicate the genomic data will determine the success of this project.

In conclusion, the IndiGen project embraces scientific technology for the advancement of Indian healthcare, ushering India towards the new gold standard of precision medicine. Policies that can enable the project to work optimally need to be framed to ensure its smooth and sustained functioning.

Shambhavi Naik is a fellow at the Takshashila Institutions Technology and Policy Programme.

Also read: Gene editing might alter our DNA, but at the cost of our humanity

ThePrint is now on Telegram. For the best reports & opinion on politics, governance and more, subscribe to ThePrint on Telegram.

Read more here:
IndiGen project how mapping of genomes could transform Indias healthcare - ThePrint

A glance around the walls of Barry J. Byrnes office reveals a lot about the pediatric cardiologist who runs thePowell Gene Therapy Center at University of Florida (UF).

In one corner is an unusual painting by 9-year-old Will Barkowsky of Jacksonville, Fla. Will, the first boy with Duchenne muscular dystrophy to takeSarepta Therapeutics exon-skipping medication Exondys 51 (eteplirsen), put together his oil-on-canvas masterpiece using the tire tracks of his wheelchair, making sure the colors didnt mix.

Nearby is a movie poster for The Ataxian an award-winning 2015 documentary by Kevin Schlanser and Zack Bennett about 17-year-old Kyle Bryant, who despite having Friedreichs ataxia embarks on a cross-country bicycle trip with three buddies.

Another movie poster advertises Extraordinary Measures, the 2010 tearjerker starring Brendan Fraser as John Crowley the father of two kids with Pompe disease and later, the founder of Amicus Therapeutics and Harrison Ford as fictional researcher Robert Stonehill, who discovers a treatment for the genetic disorder that eventually saves the lives of Crowleys children.

Theres also a model of a Blalock-Taussig shunt frequently used in congenital heart surgery, as well as one of an adeno-associated virus (AAV) vector, along with a prominent photo of Byrne with Ron Bartek, co-founder and director of the Friedreichs Ataxia Research Alliance (FARA).

Friedreichs ataxia is where were putting most of our efforts now, said Byrne, who spoke to BioNews Services publisher of this website at length during a recent visit to his lab in Gainesville, Fla.

Byrne, along with Jerry Mendell, MD, a neurologist with Nationwide Childrens Hospital in Columbus, Ohio, hosted a Nov. 20 webinar on gene therapy organized by the National Organization for Rare Disorders (NORD) and the American Society for Gene & Cell Therapy.

The two experts were introduced by Katie Kowalski, senior program manager for NORDs Educational Initiatives. The webinar, Understanding the Gene Therapy Process and Aftercare, was the fourth in a five-part series underwritten by Amicus and Sarepta, as well as two other companies, Avrobio and Bluebird Bio.

The final webinar in the series, Life After Gene Therapy, is scheduled for Dec. 18.

Mendell, who heads Nationwides Center for Gene Therapy, specializes in gene therapy research for Duchenne as well as limb-girdle muscular dystrophy, spinal muscular atrophy (SMA) and X-linked myotubular myopathy. He was a principal investigator for the Novartis therapy Zolgensma, which uses an AAV vector to carry a working version of SMN1, the mutated gene in people with SMA.

Zolgensma won approval from the U.S. Food and Drug Administration (FDA) in May 2019 as the first gene therapy to treat SMA in infants up to 2 years of age.

At $2.125 million per patient, the hour-long Zolgensma infusion is the most expensive medicine in history. The cost easily eclipses that of the only other FDA-approved treatment for SMA, BiogensSpinraza(nusinersen), which retails for $750,000 the first year and $375,000 every year after.

Many of my colleagues have been trying to make inroads for years, Mendell said. When we first got into the gene therapy domain, we were limited by technology. We could not make enough virus for the kind of impact were having now. But technology has improved, and we can now deliver genes through circulation to reach all muscles.

Regardless of the disease, he said, its extremely important to confirm the patients specific mutation before anything else.

This is critical, because you dont want to deliver the wrong kind of gene in a disease like Friedreichs ataxia. That goes for all gene therapy trials, he said. Next, we want to check for pre-existing antibodies, whether theyre acquired from the environment or from close contact. They bind to the AAV and block entry to the target organ.

Checking for those antibodies requires a blood test. It generally takes 4-7 days to return lab results a nailbiting time for patients and families, Mendell said, because theyre waiting to be approved for enrollment in the trial.

Byrne estimated that 50-60% of all individuals may have been exposed to AAV.

Prior exposure at any level to any AAV infection is an exclusion in most studies, he said, noting that people who travel frequently or who have respiratory or gastrointestinal conditions are particularly susceptible. We are learning a lot about what thresholds are effective. Its about 10% of newborns and about 50% of those of school age and adulthood.

Patients must also be in general good health except, of course, for the genetic disease being treated. MRI and blood tests are done to rule out diabetes or any evidence of heart, liver, or kidney problems.

We put the patient to sleep so theres really no pain involved, Mendell said. We also use local numbing medicine, even though the patient is asleep, so theres no pain or discomfort.

The Powell Gene Therapy Center was established in 1996 the year before Byrne joined UF by Nicholas Muzyczka, PhD, who performed groundbreaking work on AAVs in the 1980s. The center has a dozen individual labs working in neuroscience and molecular genetics.

Byrne said that because gene therapy fundamentally changes many of the bodys cells, screening is crucial.

This is often a one-way street, in that since the effects are long-lasting, other experimental studies may not accept patients who have received gene therapy of any kind in the past, Byrne said. One must have the clinical features required of the study and meet certain functional and age criteria.

To prepare for screening, patients or their parents must read the informed consent and understand what the risks and benefits are. Genetic counseling also may be required to determine whether a given mutation is amenable to gene therapy.

Baseline evaluations are done when its a muscular skeletal disease timed function tests as well as lab tests and a study schedule is established, he said. In many of our studies, we see the patients very frequently, almost every day for the first two weeks. They stay in the area for up to a month. Because were often dealing with rare populations, that makes it convenient for us to evaluate these patients.

Byrne noted that gene therapy is not necessarily durable for the lifespan of the patient. Because the delivered gene does not integrate into the cells own DNA, it is not passed down to newly formed cells.

Some cells, particularly in the liver and muscle, continue to grow throughout childhood and AAV doesnt integrate, so its progressively less effective unless the cells being targeted, as in SMA, are not dividing, he said. Thats an example where newborn screening is critically important to better outcomes.

Mendell said he generally starts patients on prednisone one day before receiving gene therapy in order to suppress liver inflammation, and keeps them on it for 60 days after.

When were in the room, the first thing that happens is the gene is delivered. You push a button and get started, he said. Obviously it must be the correct gene. Its in there, but you cant see it.

The actual gene is delivered by intravenous (IV) infusion with a pump over a 90-minute period, Mendell said; anything faster than that could potentially cause harmful side effects.

We put IVs in both arms for continuous delivery in case one side gets clogged up. We dont want anything to stop gene delivery, he said. Meanwhile, the patient is constantly monitored for vital signs. We invite the whole family to stay together, and thats reassuring. Theres anxiety about gene therapy, but the potential benefits generally outweigh any risks involved.

Some patients may develop nausea and vomiting in the first one-to-three weeks following treatment. For this reason, blood is taken every two weeks for three months to check for side effects.

Mendell said he knows patients are responding to gene therapy by doing testing. In the case of Duchenne, he uses the North Star Ambulatory Assessment, which includes 17 timed tests such as climbing stairs, rising from a sitting position, and walking or running 100 meters. In addition, neck control is a very good indicator of efficacy among Duchenne boys, he said.

The FDA anticipates that within the next 10 years, it will approve up to 40 gene therapies for rare conditions. Mendell said the benefits of gene therapy for one condition in particular, SMA, are undeniable.

This is an absolutely devastating disease. In type 1 SMA, patients usually dont survive past age 2, and about 50% are gone by age 1, he said. Initially there was concern about giving this to infants, but we told the FDA we needed to test infants in order to save lives.

Continuing results from Mendells pivotal Phase 1 trial (NCT02122952) in 15 type 1 infants and along-term extension study (NCT03421977) have changed the way people view gene therapys potential in general.

After four years, he said, every patient in our trial went from being unable to sit to being able to, and several are able to walk. One patient was treated 28 days after birth, and now four years later, hes off to school. What Barry and I do is very gratifying, and we thank our patients and their families for this opportunity.

See the article here:
Experts Barry Byrne, Jerry Mendell Lead NORD Webinar on Gene Therapy - Muscular Dystrophy News

As we stare down the barrel of the futuristic-sounding year 2020, its a time for reflection on the past decade. The world has seen some pretty major scientific achievements in the last 10 years, as discoveries and developments decades in the making were finally realized. New Atlas rounds up five of the most ground-breaking, history-making milestones of the 2010s.The Higgs boson

ATLAS Collaboration

In 2012, a new elementary particle was discovered at CERN that caught the attention of the world even those who may not normally be across particle physics news. But thats because this was no ordinary particle. This newcomer was none other than the Higgs boson.

While it may have captured the public imagination due to its dramatic but inaccurate nickname, the God particle, the Higgs boson was an incredibly exciting find for a number of reasons. It was the final elementary particle predicted by the Standard Model of particle physics, it gives mass to other elementary particles, and scientists had been hunting for it for almost 50 years.

Prior to the 1960s, the Standard Model had a bit of a problem: according to its predictions, elementary particles called bosons should have no mass but observations show they do. In 1964, three teams of scientists independently came up with similar mechanisms for how they gain mass.

According to the prevailing idea, a quantum field uniformly pervades the universe. Bosons feel this field, which slows them down and in the process, gives them mass. This field would be mediated by a brand new boson that had yet to be discovered and it wouldnt be for another 48 years.

The predicted field, mechanism and boson all eventually came to be named after Peter Higgs, one of the physicists who first proposed it.

And sure enough, in 2012 scientists at CERNs Large Hadron Collider finally found a particle consistent with the predicted properties of the Higgs boson. Further research later confirmed it to be the elusive Higgs, and two of the researchers responsible for proposing it Higgs himself and Francois Englert, a physicist on another team were awarded the 2013 Nobel Prize in Physics.

In the years since, further experiments at CERN showed that all measurements of the Higgs boson, including its spin, parity, mass and interactions with other particles, agreed with the predictions of the Standard Model.

Closing a half-century hunt for the Holy Grail of particle physics, the Higgs boson is easily one of the most important scientific achievements of the decade.

CRISPR gene-editing

The ability to edit the genes of living humans and other organisms has been a staple of science fiction for decades and this decade, it became a reality. The CRISPR gene-editing system is poised to revolutionize medicine, potentially helping us fight the big ones like cancer and HIV, as well as tackle non-health problems. But of course, its not without its controversies.

Clustered regularly interspaced short palindromic repeats (CRISPR) is a family of DNA sequences naturally used by bacteria as a self-defense mechanism. In recent years scientists realized they could co-opt this mechanism as a tool for genetic engineering, by combining CRISPR with a guide RNA sequence and an enzyme, usually Cas9.

When used in cells or living organisms, the guide RNA directs the tool to the desired section of DNA, where the Cas9 enzyme neatly cuts it. That can be used to snip out troublesome genes such as those that cause disease and insert new, beneficial ones.

So far, this technique has shown promise in fighting many different diseases, including traditionally tricky ones like cancer, HIV, muscular dystrophy, progeria, and genetic forms of blindness and heart disease.

But CRISPRs potential extends beyond editing ourselves. We can edit plants to make crops with better yields or nutrition, edit insects to stop them spreading disease, or edit pigs to grow human organs for transplant.

Of course, as promising as CRISPR seems, the tool raises ethical issues that are still in the process of being addressed. Studies have suggested that CRISPR raises the chances of a cell developing cancer down the track, and could cause unintended mutations throughout the genome. These results are hotly debated.

It all came to a head in November 2018, when Chinese scientists announced the birth of twin girls as the worlds first CRISPR-edited human babies. Professor Jiankui He and his team injected the CRISPR machinery into the embryo, deleting a gene known as CCR5. In doing so, the girls should develop an immunity to HIV.

The problem is the experiment was conducted largely in secret, sidestepping years of considered debate about ethics. Some scientists pointed out that the function of CCR5 is poorly understood, and deleting it could make the girls more susceptible to common illnesses like the flu.

After this reckless move, calls have been made for a moratorium on human germline editing until these ethical questions can be sorted out.

Despite this, CRISPR trials in humans are still going ahead just not in embryos. They began in China in 2016, in attempts to fight lung cancer, but results have yet to be published. Two trials kicked off in the US in 2019, with one targeting three types of cancer and the other sickle cell disease, with extremely promising early results.

It may have had a rocky start, but CRISPR gene-editing will likely go down in history as one of the most important breakthroughs in medicine, as well as for uses we havent even considered yet.Gravitational waves

LIGO/T. Pyle

In 2015, physicists detected ripples in the very fabric of spacetime as they washed over Earth after traveling more than a billion light years. This confirmed a prediction made by none other than Albert Einstein a century ago.

When Einstein put forward his general theory of relativity in 1916, it implied that certain events involving objects with huge masses would generate shockwaves in spacetime itself a phenomenon that came to be called gravitational waves.

Although theyre created by some of the most energetic events in the universe, by the time these waves reach Earth theyre only warping reality by less than the nucleus of an atom. That, of course, made them impossible to detect for almost 100 years until technology finally caught up.

The technology responsible is the Laser Interferometer Gravitational-wave Observatory (LIGO), housed in two huge facilities in Louisiana and Washington. Each of these twin detectors is made up of two 4-km-long (2.5-mi) tunnels in an L shape. Extremely precise instruments watch over lasers beamed down these tunnels for minuscule disturbances in the beams, which can be attributed to gravitational waves washing over the facility.

And sure enough, on September 14, 2015, both LIGO detectors picked up their first-ever signal. The waves were produced in a collision between two black holes about 1.3 billion light-years away.

Dozens of signals have poured in since that first detection, picked up by LIGO as well as the Virgo facility in Italy, which fired up in 2017. Most have been the result of two black holes merging, but others have included a black hole swallowing a neutron star, and two neutron stars colliding.

Its that lattermost scenario that gave us the most impressive fireworks show. Soon after one gravitational wave detection in 2017, observatories all around the world detected a whole host of electromagnetic signals from the same source, including light waves, a gamma ray burst, X-rays, and radio waves.

For solving a century-old mystery, the 2017 Nobel Prize in Physics was awarded to physicists Rainer Weiss, Kip Thorne and Barry Barish for their roles in the first detection of gravitational waves.

This isnt the end of the story either. LIGO received an upgrade in April 2019, with future works planned to make it even more sensitive. The KAGRA observatory in Japan is also due to join the hunt in December. Together, quieter and more distant events can be picked up, unlocking ever more mysteries of the cosmos.The exoplanet boom

ESO/M. Kornmesser

Over the course of human history, weve continuously zoomed out to get a wider view of our place in the universe. Our world expanded from one continent to the entire Earth. Then we realized Earth isnt the center of everything but just one planet of several orbiting the Sun. Eventually we discovered that even our solar system isnt special, but one of countless such others. And this decade, we got our first real look at just how many others are out there.

The first few exoplanets a planet orbiting a star other than the Sun were discovered back in the 1990s, but things didnt really pick up until the Kepler Space Telescope launched in 2009. This observatory was designed to watch 150,000 stars simultaneously, monitoring how often their light dimmed. If a regular pattern was seen, it suggested a planet was passing between the star and Earth.

Using this technique (known as the transition method), Kepler discovered over 2,600 exoplanets during its nine-year run. With help from other projects like HARPS, WASP, and TESS, that number has now grown to around 4,100. And we can infer a lot about what these worlds are like, by studying their atmospheres, composition, mass, what types of stars they orbit and how far away they are from those stars.

From this, weve learned about all sorts of incredible planets worthy of pulpy sci-fi stories. There are water worlds, pitch-black planets, and some hotter than stars. Theres a planet thats just one giant diamond, and another with clouds made of rubies and sapphires. On others it rains rocks, glass or sunscreen.

But perhaps the most intriguing exoplanets of all are those that are more Earth-like. After all, these are the best candidates for us to finally answer the question, are we alone in the universe? And it turns out, potentially habitable exoplanets are fairly common.

One of the biggest hauls came in 2017, with the discovery of seven rocky, roughly Earth-sized exoplanets orbiting TRAPPIST-1. Three of these orbit within the habitable zone of the cool red dwarf star, and follow-up studies have shown there could be significant amounts of water present, making them some of the best contenders for habitable planets outside our solar system.

And were only just beginning. Plenty more projects are set to launch in the next few years, looking for new worlds or studying known ones in detail. We wouldnt be too surprised if our next decade in review roundup includes the detection of extraterrestrial life.

NASA/Jane Peterson

It may not be the good kind of achievement, but in the past decade weve broken more climate records than at any other point in human history. As the effects of climate change became more visible, the issue really came to the forefront of the publics attention recently. New studies revealed the extent of the situation, and plans were set in motion to address it.

Overwhelming evidence shows a sharp uptick in atmospheric carbon dioxide (CO2) levels after about 1750 not-so-coincidentally, around the time of the Industrial Revolution. As a direct result, surface temperatures around the world have been steadily rising ever since, with a particularly sharp uptick occurring in the second half of the 20th century. This, in turn, is leading to a variety of run-on effects.

While weve known about it for a long time, climate change has dominated this decade in science, as tangible consequences begin to flare up. According to NASA and NOAA, 2016 was the hottest year since records began in 1880, and the top five are the last five. July 2019 holds the record for hottest month.

Other recent studies have revealed just what this excess heat is doing to the world. A State of the Climate report for 2018 showed that extreme weather events like hurricanes, floods, droughts and wildfires are becoming more intense and common. Glaciers and polar ice are shrinking, and sea levels are rising.

In 2015, atmospheric CO2 climbed above 400 parts per million for the first time in about three million years. This also means the oceans are absorbing more of the gas, making them more acidic. The combination of warmer and more acidic waters saw Australias Great Barrier Reef hit with back-to-back bleaching events in 2016 and 2017. While its gone through similar trauma in the distant past, experts believe the current changes struck too quickly for the Reef to fully recover from.

But theres still hope. In 2015, almost 200 countries signed onto the Paris Agreement, pledging to cut back on greenhouse gas emissions in order to keep global temperatures from rising 2 C (3.6 F) above pre-industrial levels. Reports from the Intergovernmental Panel on Climate Change (IPCC) say that to meet those goals, unprecedented changes will be needed in all aspects of society and if 2019s climate strikes and protests are any indication, society is warming up to the idea.

That wraps up our take on the five most significant scientific achievements of the decade but there are of course other candidates. So what get's your vote? Let us know in the comments below.

Go here to read the rest:
The 5 most groundbreaking scientific achievements of the decade - New Atlas

BEDFORD, Mass., Nov. 26, 2019 (GLOBE NEWSWIRE) -- Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today a peer-reviewed publication demonstrating its proprietary adeno-associated viral vectors (AAVHSCs) crossed the blood-brain-barrier and blood-nerve-barrier in non-human primates (NHPs), highlighting their potential to deliver gene therapy for central and peripheral nervous system disorders.

The publication includes the initial characterization of biodistribution with three of Homologys 15 AAVHSCs, including their ability to transduce, or target, key cells following a single intravenous (I.V.) administration in NHPs. AAVHSCs are naturally occurring vectors originally isolated from human hematopoietic stem cells.

Many neurological diseases, including lysosomal storage and neuromuscular disorders, have cognitive and systemic components requiring a genetic medicine to reach multiple tissues to target the disease-relevant cell types, said Albert Seymour, Ph.D., Chief Scientific Officer of Homology Medicines. Here we evaluated the ability of three of our novel AAVHSCs to cross the blood-brain-barrier and the blood-nerve barrier after I.V. administration in NHPs in addition to other key tissues, which allows us to choose the vectors best suited for particular diseases. We have observed that small sequence changes among our family of AAVHSCs are associated with differences in their ability to target disease-relevant tissues. We continue to characterize these properties and the potential of AAVHSCs as vehicles for therapeutic delivery.

Following I.V. administration of AAVHSC -7, -15 and -17 in NHPs, analyses showed transduction and transgene expression:

The publication, Clade F AAVHSCs Cross the Blood Brain Barrier and Transduce the Central Nervous System in Addition to Peripheral Tissues Following Intravenous Administration in Nonhuman Primates, was peer-reviewed and published in the journal PLOS ONE. For more information, please visithttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225582or http://www.homologymedicines.com/publications.

About Homology Medicines, Inc. Homology Medicines, Inc. is a genetic medicines company dedicated to transforming the lives of patients suffering from rare genetic diseases with significant unmet medical needs by curing the underlying cause of the disease. Homologys proprietary platform is designed to utilize its human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to precisely and efficiently deliver genetic medicinesin vivoeither through a gene therapy or nuclease-free gene editing modality across a broad range of genetic disorders. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a particular focus on rare diseases, and intellectual property covering its suite of 15 AAVHSCs. Homology believes that its compelling preclinical data, scientific expertise, product development strategy, manufacturing capabilities and intellectual property position it as a leader in the development of genetic medicines. For more information, please visitwww.homologymedicines.com.

Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding our expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of our product candidates; beliefs about preclinical data and the properties and potential of our AAVHSCs; and our position as a leader in the development of genetic medicines. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; failure to identify additional product candidates and develop or commercialize marketable products; the early stage of our development efforts; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the capabilities and potential expansion of our manufacturing facility; risks relating to the regulatory approval process; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; failure to obtain U.S. or international marketing approval; ongoing regulatory obligations; effects of significant competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; failure to attract, retain and motivate qualified personnel; the possibility of system failures or security breaches; risks relating to intellectual property and significant costs as a result of operating as a public company. These and other important factors discussed under the caption Risk Factors in our Quarterly Report on Form 10-Q for the quarter endedSeptember 30, 2019and our other filings with theSECcould cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent managements estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

Go here to see the original:
Homology Medicines Announces Peer-Reviewed Publication Demonstrating its AAVHSC Vectors Crossed the Blood-Brain-Barrier and Blood-Nerve-Barrier in...