NightstaRx and The University of Alberta announce the start of the first Canadian gene therapy study to treat Choroideremia

NightstaRx Ltd (“Nightstar”), the biopharmaceutical company specialising in bringing therapies for retinal dystrophies to patients, announces that the University of Alberta, has begun enrolling and dosing subjects in a Phase II clinical trial of the Company’s gene therapy for the treatment of choroideremia (CHM). This gene therapy approach uses a viral vector known as adeno-associated virus (AAV) to deliver a wild-type copy of the Rab-escort protein 1 (REP-1) gene (AAV2-REP1) into cells of the eye.

The trial, which is sponsored by the University of Alberta, is an open label study involving a total of 6 male patients, who will each receive a single dose of AAV2-REP1 via a sub retinal injection.

Choroideremia is an inherited X-linked recessive disease which inevitably causes blindness. It is caused by mutations to the CHM gene which encodes Rab-escort protein 1 and affects approximately 1 in 50,000 people. The first symptom of the condition is usually an impairment of night vision which often occurs in early childhood. This is followed by progressive narrowing of the field of vision, as well as a decrease in the ability to see details, culminating in blindness, most commonly in late adulthood. No effective treatment currently exists.

David Fellows, CEO of Nightstar said:
“Gene therapy treats genetic diseases at the molecular level by correcting what is wrong with defective genes. We are broadening our pipeline of products in development and are leading the way in the development of an effective gene therapy treatment for choroideremia. This new study, sponsored by the University of Alberta, is another step forward in the development of AAV2-REP1. We have been granted Orphan Drug Designation for the product in the United States and Europe and the data to date has shown very promising results.”

Ian MacDonald, Professor of Ophthalmology and Visual Sciences, University of Alberta commented:
“We are very excited to be working with Nightstar and to have treated our first choroideremia patient. Choroideremia is a devastating condition for individuals and families, but we believe our new gene therapy will arrest any further deterioration of vision and will provide long lasting benefit. The next challenge will be making this therapy available to all individuals with the condition as soon as we possibly can.”

About Choroideremia

Choroideremia is an inherited disorder that leads to progressive loss of vision due to degeneration of the choroid and retina which is caused by a lack of Rab Escort Protein-1 (REP-1) and occurs almost exclusively in males. The first symptoms occur in childhood, with night blindness being the most common first symptom. As the disease progresses, there is loss of peripheral vision or ‘tunnel vision’, and later a loss of central vision. Progression of the disease continues throughout the individual’s life, although both the rate and the degree of visual loss can vary, even within the same family. There is currently no treatment or cure for this disease.

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More than 95% of the global population has at least one health problem, study finds

The largest and most in-depth study of global health trends to date finds that more than 95% of the world’s population has health problems, with more than a third of us experiencing five or more conditions.

The results of the Global Burden of Disease Study 2013 (GBD 2013) were recently published inThe Lancet.Lead study author Prof. Theo Vos, of the Institute of Health Metrics and Evaluation at the University of Washington in Seattle, and colleagues set out to calculate up-to-date estimates of disease and injury incidence and prevalence among 188 countries between 1990 and 2013, using data from more than 35,000 sources.

The team also sought to estimate the number of disability-adjusted life years (DALYS) – that is, the number of healthy years lost due to illness – over the 23-year period.In total, the researchers were able to provide global estimates of incidence and prevalence for 301 acute and chronic diseases, and they were able to assess the effects of 2,337 health consequences that result from at least one of these disorders.

Prof. Vos and colleagues found that in 2013, only 1 in 20 people (4.3%) around the globe had no health problems, meaning more than 95% of us had one or more illnesses.

The researchers found that 2.3 billion people worldwide – more than a third of us – had at least five health conditions in 2013. Over the 23-year study period, the number of people with 10 or more health conditions rose by 52%.

The number of people with multiple illnesses increased with age. In 2013, 36% of children in developed countries aged 0-4 years had no illnesses, compared with only 0.03% of adults aged 80 and older.

The number of healthy years lost due to illness increased from 21% in 1990 to 31% in 2013, and the number of years lived with disability (YLD) rose from 537.6 million in 1990 to 764.8 million in 2013.

The researchers attribute the increase in YLD over the 23-year period to population growth and aging. They found that the main drivers for YLD were musculoskeletal disorders, mental illnesses, substance abuse disorders, neurological conditions and chronic respiratory disorders.

Disability rates not declining as fast as death rates

The leading causes of health loss did not change much between 1990 and 2013, according to the researchers.

They found that in 2013, musculoskeletal disorders, such as low back pain and arthritis, and mental and substance use disorders – particularly anxiety, depression and drug and alcohol use disorders – accounted for almost 50% of all health loss globally.

Low back pain and major depression were ranked as two of the top 10 disability contributors in 2013 among every country. These conditions caused more health loss than chronic obstructive pulmonary disease (COPD), diabetes and asthma combined, according to the results.

The team found the leading causes of disability and health loss varied by regions. Falls, for example, were found to be the second leading cause of disability in 11 of 13 countries in central Europe, while anxiety disorders were more prominent causes of disability in Caribbean regions.

Past war conflict was identified as the main contributor to health loss in Cambodia, Nicaragua, Rwanda, while ranking as the second leading cause of health loss in Vietnam.

Perhaps one of the most important findings was that rates of disability as a result of health problems are not declining as rapidly as death rates from such conditions. The team points to diabetes as an example; while diabetes rates rose by 43% between 1990 and 2013, death rates from the condition only increased by 9%.

“The fact that mortality is declining faster than non-fatal disease and injury prevalence is further evidence of the importance of paying attention to the rising health loss from these leading causes of disability, and not simply focusing on reducing mortality,” says Prof. Vos, adding:

“Large, preventable causes of health loss, particularly serious musculoskeletal disorders and mental and behavioral disorders, have not received the attention that they deserve. Addressing these issues will require a shift in health priorities around the world, not just to keep people alive into old age, but also to keep them healthy.”

The Bill and Melinda Gates Foundation funded the study.

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McMaster researchers test fecal transplantation to treat ulcerative colitis

Two new studies led by researchers from the Farncombe Family Digestive Health Research Institute at McMaster University show that transplantation of fecal matter may be a useful tool in the fight against ulcerative colitis (UC).

Ulcerative colitis is a chronic, debilitating inflammatory bowel condition characterized by symptoms including bloody stools, diarrhea, abdominal pain, weight loss and malnutrition. It results from the development of abnormal immune responses to the normal bacteria in the digestive tract. It is difficult to treat and standard therapy doesn’t always work.

There is currently great interest in treating UC with fecal microbiota transplantation (FMT), which involves transplanting gut fecal bacteria from healthy people into patients with UC.

A study recently published in Inflammatory Bowel Diseases found that UC can be controlled by the type of bacteria that inhabits the gut. The study was led by Elena Verdu, an associate professor of medicine with the Michael G. DeGroote School of Medicine.

“Our animal research provides insight that selected bacterial groups, involved in gut health, are important for protecting the colon against injury and inflammation,” said Verdu.

Along the same theme, in research published on June 29, 2015 in Gastroenterology, professor of medicine Paul Moayyedi and his team explored the safety and efficacy of FMT by conducting a placebo-controlled, randomized trial. They found that “FMT induces remission in a significantly greater percentage of patients with active UC than placebo,” the authors wrote.

“Our study in patients with ulcerative colitis is the first randomized trial of fecal microbiota transplantation in adults with ulcerative colitis and shows that this therapy may work,” said Moayyedi. “The effect of fecal transplant seems to be dependent on the sort of bacteria that is in the donor stool, which fits with the observations of Dr. Verdu’s animal study.”

In Verdu’s study, mice were given gut bacteria from patients with severe UC and the effects were compared to those produced in mice that were given bacteria from a healthy person. The results identified a reduced amount of the bacterial families that are important for gut health in the feces of patients with severe colitis.

Second, they found that when mice were given these bacteria and then exposed to a toxin that causes gut injury, the resulting inflammation was higher in the mice with UC bacteria than in mice with bacteria from the healthy person, in whom the beneficial bacterial groups were abundant.

“The study also showed that the same protective effect could be achieved using the fecal material from the healthy person as with specific groups of bacteria that were isolated from the ‘healthy’ fecal matter,” said Verdu. “This suggests that specific combinations of beneficial bacteria extracted from healthy people could be tested in future clinical fecal transplantation studies, and could potentially replace fecal matter.”

Verdu said the implications of her study relate to the selection of healthy donors for fecal transplantation.

“In addition to screening for infections and disease, donors that harbour an abundance of the beneficial bacterial groups identified in our study could be selected to increase the chances of success of transplantation,” said Verdu.

Moayyedi and his team, including McMaster professors Michael Surette and Christine Lee, recruited 75 patients with a flare up of their UC and randomized them to fecal transplant therapy given as an enema derived from stool donated by an anonymous healthy donor once per week for six weeks, or a placebo consisting of a water enema. They found 24 per cent were in remission in the fecal transplant group compared to five per cent in the placebo group. There were two main healthy donors, donor A and donor B – one of which was the healthy donor from Verdu’s mouse study – and benefit seemed to be mostly related to those that received stool from donor B. The effect was also greater in those that had recently been diagnosed with UC.

“Many questions remain, but this provides interesting data suggesting that altering the gut microbial flora may be promising for treating ulcerative colitis,” the authors noted.

Moayyedi added that the data suggests more research is needed using the FMT approach.

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FDA strengthens heart safety warnings on painkillers

People should think carefully about taking these drugs, both over-the-counter versions and prescription pills, the FDA says. It’s asking manufacturers to change the labels.”They used to say they might cause risk of heart attack or stroke. Now we are saying they do cause increased risk of heart attack and stroke,The warning covers drugs called nonsteroidal anti-inflammatory drugs or NSAIDS for short. They include ibuprofen, sold under brand names like Advil or Motrin; naproxen (Aleve), as well as prescription arthritis drugs known as COX-2 inhibitors, such as Celebrex. Tylenol, known generically as acetaminophen, is not an NSAID.Cough and cold remedies can also contain NSAIDs as an ingredient.”Because many prescription and OTC medicines contain NSAIDs, consumers should avoid taking multiple remedies with the same active ingredient,” the FDA said.

“FDA is strengthening an existing warning in prescription drug labels and over-the-counter (OTC) Drug Facts labels to indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) can increase the chance of a heart attack or stroke, either of which can lead to death,”

“Those serious side effects can occur as early as the first few weeks of using an NSAID, and the risk might rise the longer people take NSAIDs. (Although aspirin is also an NSAID, this revised warning doesn’t apply to aspirin.)”

Last year, FDA said it was reviewing the safety of these drugs.

Some of the studies they looked at showed a clear pattern: people who took NSAIDS were more likely to have heart attacks or strokes.

“There is no period of use shown to be without risk,” said Dr. Judy Racoosin, deputy director of FDA’s Division of Anesthesia, Analgesia and Addiction Products.”In the coming months, the FDA will request that manufacturers update the existing cardiovascular risk information in Drug Facts labels for over-the-counter (OTC) non-aspirin NSAIDs. Consumers and health care professionals should remain alert for the development of heart- and stroke-related symptoms throughout the time a consumer takes any NSAID,” FDA said.This doesn’t mean people should just stop taking NSAIDS, FDA said.”Take the lowest effective dose for the shortest amount of time possible,” said FDA’s Dr. Karen Mahoney.The American Heart Association advises people to try acetaminophen (Tylenol) first.

“If you have heart disease or high blood pressure, consult a health care provider before using an NSAID,” FDA added.

“Balance the benefits of NSAIDs with the possible risks and weigh your options. If you take low-dose aspirin for protection against heart attack and stroke, you should know that some NSAIDs, including ibuprofen and naproxen, can interfere with that protective effect.”

And the agency gives advice on what symptoms to look for.

“Stop taking NSAIDs and seek medical help if you experience symptoms that might signal heart problems or stroke, such as chest pain, trouble breathing, sudden weakness in one part or side of the body, or sudden slurred speech.”

In 2013 Americans bought more than 275 million boxes of over-the-counter NSAIDs, racking up $1.7 billion in sales, according to retail tracker IRI.

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FIRST EVER INHALABLE EBOLA VACCINE IS SUCCESSFUL IN SIMIAN TRIALS.

July 14, 2015

A collaborative team from The University of Texas and the National Institutes of Health have developed an inhalable vaccine that successfully protects primates against Ebola in simian trials. The team state that a needle-free, inhalable vaccine against Ebola presents certain advantages as it has been shown that this disease lines respiratory tract in infection, also, this will mean that immunization will not require trained medical personnel.  The opensource study is published in theJournal of Clinical Investigation.

Previous studies with primates suggest that aerosols of most biothreat agents, which are particles dispersed in the air, are infectious. Recent studies show that contact with the Ebola virus through the mucus membranes that line the respiratory tract results in infection, suggesting that airway linings may be important portals of entry for the virus. Aerosolized delivery has never before been tested for an Ebola vaccine or any other viral hemorrhagic fever vaccine.

The current study characterized the immune responses generated by vaccination against Ebola delivered to the respiratory tract as either an aerosol or liquid. Direct comparisons were made with an unrelated protective injectable Ebola vaccine. This included detailed comparisons between immune T cell responses in the lungs, spleen and blood. A single vaccination with the aerosol developed by the researchers protected non-human primates against the severe disease and death caused by lethal Ebola infection.

The team state that this study demonstrates successful aerosol vaccination against a viral hemorrhagic fever for the first time.  They go on to add that a single-dose aerosol vaccine would enable both prevention and containment of Ebola infections, in a natural outbreak setting where healthcare infrastructure is lacking or during bioterrorism and biological warfare scenarios.

The researchers surmise that the findings of this study provide the basis for advancing this experimental vaccine to an NIH phase I clinical study. They go on to conclude that in the future, pending approval through an Investigative New Drug Application, the aerosolized form of the vaccine will be evaluated for replication, safety and immunity development in a study in adults.

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 Source: The University of Texas Medical Branch

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FIRST PATIENT IN THE WORLD BRIDGED TO A SUCCESSFUL HEART TRANSPLANT VIA A TOTAL ARTIFICIAL HEART.

A petite 44-year-old woman has become the first patient in the world to be bridged to a successful heart transplant, that is, to go from needing a transplant to receiving one, with an experimental Total Artificial Heart designed for smaller patients.  The UCLA patient received a successful heart transplant at Ronald Reagan UCLA Medical Center, thanks to the smaller Total Artificial Heart.

The team explain that the 50cc SynCardia temporary Total Artificial Heart is a smaller investigational version of the larger 70cc SynCardia heart, which was approved for use in people awaiting a transplant by the Federal Food and Drug Administration in 2004 and has been used by more than 1,440 patients worldwide.  They go on to add that the 50cc device is designed to be used by smaller patients, including most women, some men and many adolescents, with end-stage biventricular heart failure, where both sides of the heart are failing to pump enough blood to sustain the body. The device provides mechanical support until a donor heart can be found.

Nemah Kahala, a wife and mother of five, was transferred to UCLA from Kaiser Permanente Los Angeles Medical Center in March. She was suffering from restrictive heart muscle disease and in critical condition. Her heart failure was so advanced that repair surgery and other mechanical assist devices could not help.  Nemah was placed on a life support system called extra corporal membrane oxygenation, however, the team note that this only works for about 10 days before a person’s organs begin to deteriorate.

With the clock ticking, doctors needed to buy time by replacing Nemah’s failing heart with an artificial heart while she waited for a heart transplant. Her chest cavity was too small for her to receive the larger 70cc artificial heart. However, under a one-time emergency use permitted under FDA guidelines, her doctors were able to implant the experimental 50cc device.

Her surgeons explain that Mrs. Kahala’s condition was deteriorating so rapidly that she would have not survived while waiting for a transplant. The team were therefore grateful to have this experimental technology available to save her life and help bridge her to a donor heart.

The researchers state that the artificial heart provides an immediate and safe flow of blood to help vital organs recover faster and make patients better transplant candidates.  After the two-hour surgery to implant the artificial heart, Nemah remained hospitalized in the intensive care unit and eventually began daily physical therapy to help make her stronger for transplant surgery.

Two weeks after the total artificial heart surgery, she was strong enough to be placed on the heart transplant list. After a week of waiting, a donor heart was found.

In addition to the high-tech medicine that kept the patient alive, Mrs. Kahala and her family have exemplified how a solid support system that includes loved ones and a compassionate medical team practicing what we at UCLA have termed ‘Relational Medicine’ plays an important role in surviving a medical crisis.

Since 2012, the UCLA Heart Transplant Program has implanted eight 70cc SynCardia Total Artificial Hearts. UCLA also participated in the clinical study of a 13.5-pound Freedom portable driver, a backpack-sized device that powers the artificial heart, allowing the patient to leave the hospital , that received FDA approval on June 26, 2014.

Nemah was discharged from UCLA on April 18. She is grateful to be home in Riverside with her family, who own a grocery store in the city of Orange.

The SynCardia Total Artificial Heart, at left, and a human heart, at right. Credit: SynCardia 2015

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Source:  UCLA university of California 

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