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.

---

 Source: The University of Texas Medical Branch

Read More

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

---

Source:  UCLA university of California 

Read More

THE TOP TEN HEALTH INNOVATIONS OF 2014.

A great year for health innovations with exciting discoveries, verification, validations and breakthroughs.  The big disease areas are still cancer, heart disease, diabetes and Alzheimer’s, however, it’s the methodology of detection, imaging, and the descriptive diagnostics that have been innovated this year.  In some cases these disciplines and techniques bleed through to multiple disease areas as other teams pick up the technology.  A common thread running through all of these areas however, is the all important biomarker.  And with each newly discovered biomarker comes the benchmark and standardisation. A new receptor, more inroads in stem cell technology and regenerative medicine, all leading back to control and revamping of our own DNA and a big push in immunology.

We saw the definitive breakthrough that is precision genetics with the evolution of personalized medicine into precision medicine; becoming more precise and honed, moving into master regulator genes as opposed to the confusing multiple loci and the personal immunity simulation of the past.  The medical community theorizing and validating that the mass of loci being targeted were in fact the resulting cascade of these precisely hit master genes.  This big push in genetics with researchers giving clarification, gaining a clear direction in sequencing and beginning to classify epigenetic methylation.

With epigenetic methylation research teams are now beginning to map and classify cancer via the epigenome. Reaching the source of all disease, that moment of mutation, the moment of epigenetic methylation; that clear crystalline moment when disease is born.  Medical teams around the world have summised that all disease comes from nuclei, is ordered by the gene and transcribed through the MiRNA; still an important area, to the moment of epigenetic methylation.  The moment that our DNA is changed forever and the cascade of disease-causing loci and proteins begin.

Health innovators have also taken a step back even further in the source and began to chip away at the facade of neurogenetics.  The genetic code held in our brain, the regulator of not only diseases and disorders of the brain but also  disease within the body.  This leads on nicely to the great inroads being made in neuroinnovations, standardised and medicalised, this area holds many answers to the questions the medical community have been asking for decades.  When we finally map every circuit, every pathway, all neurogenetics, it is expected to lead to the man-made regulation of all disease.  And with neuroscience this need not always be invasive.

Neuroinnovations have been astounding this year with multiple validated studies medicalising diagnostics, representing disease of the brain in terms in which all disease should be presented, in scans, in blood work, in genetic terms.  We have also witnessed a big drive to uncover more about the role the lesser-known cells, such as Astrocytes, play in the brain as well as the surrounding microglia in the hope this will lead to a crack in the looming blood-brain-barrier.  And most importantly the medical community has been given more control over the disorders we now understand to be more than emotive figments of imagination; more control to help with tangible and very real mental disorders which have now been imaged, seen with the naked eye in blood work and designated the correct biomarkers.

So, what were the biggest healthinnovations of 2014? What did health innovators concur on this year?  Which disease areas, disciplines and techniques were of the most interest to health innovators across the globe and were seen as the biggest breakthroughs, raising the most interest?

So here you go health innovators, here are the Top 10 Healthinnovations of 2014 based on the total number of views and shares:

1.  At number one we have the Karolinska Institutet of Sweden, whose breakthrough

neuroscientific human study lays the foundation for neurogenetic study in neuroplasticity.  This study identified the cells responsible for the superior plasticity of the human brain, the oligodendrocyte otherwise known as myelin.  Here we saw researchers modulate myelin production, with potential to fight TBI, MS, enhance plasticity, enhance brain processes, memory, fight dementia, whilst opening a door to neuroprotection.  Neurologically-wise this study has it all.  We are seeing a sharp increase in non-neuronal studies in the brain with researchers investigating the role of these lesser-known brain cells.  The number one study also provides detailled knowledge on the brain cell in question, oligodendrocytes.  They were able to establish, through, histological studies that at birth most oligodendrocytes are immature. The study then goes on to tell us what age we are when oligodendrocytes reach maturity and their turnover rate thereafter. The researchers were even able to carbon-date the cells and determine their age which is why this is the most viewed and shared Healthinnovations of 2014.

2.  At number two we have is the National University of Singapore of Singapore, who found a new type of immune cell that is expected to help in the development of a future treatment for Multiple Sclerosis (MS).  The study also explores the role of the all-important interleukin pathway, a very hot area at the moment, in the immune system.  The team found that a new type of immune T helper cells named TH-GM cells play a crucial role in the immune system and pathogenesis of neuronal

inflammation. The team showed that STAT5, a member of the STAT family of proteins, programs TH-GM and initiates the immune response to an auto-antigen in responding to a signal from an interleukin, IL-7, causing neuroinflammation, pathogenesis and damage in the central nervous system. Thus blocking IL-7 or STAT5 would provide a significant therapeutic benefit for Multiple Sclerosis (MS).

3.  Coming in next at number three St Vincent’s Hospital and the Victor Chang Cardiac Research Institute of Australia, who transplanted an already dead heart in a world’s first.  This breakthrough firmly pushed the human race out of the age of regeneration hurtling into the aeon of reanimation.  Surgeon’s developed a technique which means hearts that had been still for 20 minutes can be resuscitated and

transplanted into a patient.  The technique involves donor hearts being transferred to a portable machine known as a ‘heart in a box’ in which they were placed in a preservation solution, resuscitated and kept warm.  So far three people have received hearts in this way, with this novel transplant system expected to save 30 percent more lives by providing more hearts, which were in the past deemed unsuitable and/or too starved of oxygen to transplant.

4.  At number four is the Hebrew University of Jerusalem of Israel and the Max Dellbruck Institute of Germany.  The team not only discovered how the recently discovered circular RNA is formed they also identified a key muscular dystrophy link.  Unlike all other known RNAs, this molecule is circular, and is labelled circular RNA.  The team found that circRNAs not only compete with normal

RNAs, but the body actually produces them at the expense of normal RNA. The researchers observed that circRNAs play an important role in brain function, and likely in brain disease.  In addition, the researchers identified the protein ‘muscleblind’ as a factor involved in circRNA biogenesis, and showed that muscleblind can enhance and regulate the production of a subset of circular RNAs.  Importantly, defects in muscleblind function are known to cause a severe degenerative disease called myotonic dystrophy. Characterized by progressive muscle wasting and weakness, this is the most common form of muscular dystrophy that begins in adulthood.

5.  At the midway mark, at number five, we have the University of California, Los Angeles (UCLA), of the United States of America.  The team utilized a novel technology called electric field-induced release and measurement (EFIRM) to test lung cancer patients’ saliva for epidermal growth factor receptor (EGFR) gene mutations, a sign of lung cancer, which can be treated by medication

such as thymidine kinase inhibitors. The total detection time is less than 10 minutes and only requires a small saliva sample.  EFIRM is a multiplexible electrochemical sensor which uses electrode chips to enable exosomes in saliva to rapidly release molecular constituents (DNA, RNA and proteins) while simultaneously detecting any mutations in tumour-causing DNA sequences.  So here is a cancer detection study hitting all the marks, precision genetics, non-invasive testing, epigenetic mutation/methylation markers for cancer and a new spectra method. And of course that all important new biomarker.

6. Coming in at number six we have a multi-centre study led by the University of California of the United States of America.  This study reminded the medical community how important verification

and building on initial discovery is in making past findings standardised for usage in mass clinical settings.  Here the team provided the first evidence of the medium- to long-term safety and tolerability of transplanting human embryonic stem cells (hESCs) in humans.   This important benchmark also provided set hESCs dosages when treating human macular degeneration with stem cell therapy.

7.  At number seven we have the University of Connecticut, of the United States of America.   The team found a new way to identify protein mutations in cancer cells to develop the first precision medical vaccine to treat patients with ovarian cancer.  This vaccine is so precise that it can recognise tiny differences and mistakes on a cancer cell’s surface epitopes, thus allowing the cancer ‘vaccine’ to attack and kill the cancer cell.  In this way the

surrounding healthy cells with normal epitope sequences are ignored and left intact.  These subtle epitope mutations come from incorrect epigenetic methylation when cancer cells proliferate, making this a best-in-class when it comes to precision genetics and medicine.

8.  Nearing the end of this great list we have the Lund University of Sweden, McGill University of Canada and theHeart and Stroke Foundation of Canada at number eight.  This large-scale study  linked the genetic predisposition to elevated low-density lipoprotein cholesterol (LDL-C) to aortic

valve calcium and narrowing of the aortic valve.  This study was also valuable due to the fact there are 35,000 participants providing strong, instant validation for this new discovery.  Any team in the future will find validation an easy job with this study giving it an easy path into clinical procedure.  The data suggests that, in addition to the established risks for myocardial infarction and other vascular diseases, increases in low-density lipoprotein cholesterol are also associated with increased risk for aortic stenosis.  The team now plan to investigate whether intervention to reduce low-density lipoprotein cholesterol could prevent aortic valve disease.

9.  At number nine of the Top Ten Health innovations of 2014  we have the Salk Institute and Harvard Medical School of the United States of America.  Very few studies assimilate the spinal

chord and brain as one entity let alone map new spinal chord-to-brain neural mechanisms and receptors for chronic pain.  The researchers set out to precisely identify the spinal neurons involved in these circuits. They deciphered the role each of the two neuronal cell types, pain receptors and touch receptors, play in the processing of pain signals in the dorsal horn, the location where the sensory neurons connect with the spinal chord. The findings of this study are expected to help find new targets and treatments for the people who suffer from chronic pain as well as allodynia, fibromyalgia and nerve damage caused by diseases such as diabetes, cancer and autoimmune disorders as well as physical trauma.  As new technology and diagnostics become more available to the neuroscientific community these rich neurobiological studies, whereby more vital neuroanatomy is discovered, are greatly anticipated and received.

10. And at number ten we have Boston University of the United States of America and the United States Army, with a genetically-based breakthrough for Ebola.  One of the greatest concerns about this killer disease is the conjecture over the time of contagion.  The general consensus is that

Ebola only becomes contagious once a fever breaks with opponents stating that this is only because the fever is the onset of vomiting, unexplained bleeding and/or diarrhea, ie. excessive bodily fluid-loss.  Thus the existing argument is that although the incubation period of Ebola can be as long as three weeks, this excessive loss of Ebola-infected bodily fluid grossly raises the level of potential contamination and infection.  The researchers put paid to this argument by providing an RNA-based assay which can distinguish between different hemorrhagic fevers, including Marburg (Ebola cousin) and Lassa before the person becomes symptomatic, at the point the virus enters the blood stream.  As the test includes the cousin of the Ebola hemorrhagic virus, the Marburg hemorrhagic virus, it is hoped that the test can be tweaked to include Ebola.

Read More

New Heart Drug From Novartis Gets FDA Approval — Now The Major Pricing Battle Begins

It used to be that the major hurdle in getting a new drug approved was successfully completing phase 3 trials – the long-term studies needed to prove to regulators that your drug was both effective and safe. These trials can take years to run and cost hundreds of millions of dollars. Yet, despite doing successful studies for many years in preparation for phase 3, these late stage studies are not guaranteed to be successful. Many a phase 3 program has gone down in flames despite promising earlier trials. Thus, the successful completion of phase 3 and ultimately, approval of the drug by the FDA, is the cause of jubilation at the sponsoring company and especially by the hundreds of people involved in completing the successful program.

This is likely what happened yesterday at Novartis when it received FDA approval for its new drug to treat heart failure, Entresto (previously known by its code name LCZ696). This drug is the first of a new class called angiotensin receptor neprilysin inhibitors. In its development of Entresto, Novartis carried out an extensive clinical plan, the cornerstone of which being PARADIGM, an 8,442 patient trial of people with heart disease in which half of the patients received the Novartis drug and the other half received enalapril, a generic drug that is the current standard of care. The results of the trial proved remarkable as Entresto showed a 20% reduction in the risk of death from cardiovascular causes or hospitalization for worsening heart failure.

Novartis’ clinical plan was a risky one in that PARADIGM was designed to compare its drug against standard of care. Oftentimes, pharmaceutical companies are criticized for running clinical trials designed to make their drug look as good as possible by picking either a placebo or a weak drug as the comparator. That was not the case here. Furthermore, this was an expensive roll of the dice for Novartis as this trial likely cost hundreds of millions of dollars to run with no guarantee of success. But, by setting such a high bar for their drug with PARADIGM, they carried out the type of study that patients and physicians need by utilizing the drug in a real world setting and comparing it to the best treatment. The reward can be found in the response of cardiologists such as Clyde Yancy, the chief of cardiology at Chicago’s Northwestern Memorial Hospital who told the Wall Street Journal that Entresto is “one of the few times that we have identified a medication that is better than the standard. It’s clearly superior to what we have.” This is how clinical trials should be run and MUST be run in order to prove the value of a new drug to the world.

Normally, that would be the end of the story. But another hurdle now looms in the form of payers. Novartis has set a price of $12.50/day for Entresto (about $4,500/year). This is a far cry from the costs of breakthrough cancer or hepatitis C medications, which can often exceed $100,000/year. Novartis estimates that over 2 million Americans should be eligible for this drug and one quickly comes to the realization that this is going to be a multibillion dollar revenue generator for Novartis. Payers, however, are also painfully aware of this and might be reluctant to add another new drug to their cost basis. So now a new battle faces Novartis: convincing payers to allow access to this drug for patients in their healthcare systems. Despite the fact that Entresto is a drug that will allow heart failure patients to live longer and avoid hospitalizations, Novartis is now in discussions to justify the price of the drug with respect to the overall benefits to patients and the saving of downstream healthcare costs. In other words, it will be awhile before many heart failure patients will get access to this important medicine.

Getting FDA approval for a new important drug is always a wonderful event. Just as important in this new world of healthcare is getting “approval” of the payers – an approval that is proving challenging.

---

source : Forbes.com

Read More

Cancer patients treated in world-first clinical trial of Canadian viral therapy

Canadian researchers have launched the world’s first clinical trial of a novel investigational therapy that uses a combination of two viruses to attack and kill cancer cells, and stimulate an anti-cancer immune response. Previous research by this team and others worldwide suggests that this approach could be very powerful, and could have fewer side effects than conventional chemotherapy and radiation, although it will take years to rigorously test through this trial and others.

The therapy was jointly discovered and is being developed by Dr. David Stojdl (Children’s Hospital of Eastern Ontario, University of Ottawa), Dr. Brian Lichty (McMaster University) and Dr. John Bell (The Ottawa Hospital,University of Ottawa), and their respective research teams and colleagues. The clinical trial, which is funded by the Ontario Institute for Cancer Research and coordinated by the NCIC Clinical Trials Group, is expected to enroll up to 79 patients at four hospitals across Canada. Up to 24 patients will receive one of the viruses and the rest will receive both, two weeks apart.

Christina Monker, 75, a former nurse from Rockland, Ontario, is one of the first patients treated in the trial. She was diagnosed with cancer in 2012 and, despite six weeks of radiation therapy and two rounds of chemotherapy, the cancer spread to both her lungs. After completing another 30 rounds of chemotherapy, she enrolled in the trial at The Ottawa Hospital and was treated on June 2, 2015.

“The nausea of chemotherapy was worse than I ever could have imagined, but with the viral therapy I just felt like I had the flu for a couple of days, and the symptoms were easily managed,” said Ms. Monker. “It is too soon to know if I may have benefited from this therapy, but I’m very glad to contribute to this important research that could improve care for others.”

The idea of using viruses to treat cancer has been around for more than a century, with sporadic reports of cancer patients experiencing remarkable recoveries after viral infections. However, it is only in recent years that viral therapy has begun to be developed and tested in a rigorous way. Drs. Bell, Lichty and Stojdl began investigating viral therapies for cancer nearly 15 years ago when they worked together at The Ottawa Hospital.

“We found that when normal cells become cancerous, it’s like they are making a deal with the devil,” explained Dr. Bell, a senior scientist at The Ottawa Hospital and professor at theUniversity of Ottawa. “They acquire genetic mutations that allow them to grow very quickly, but these same mutations also make them more susceptible to viruses.”

The two viruses being tested in this clinical trial are called MG1MA3 and AdMA3. MG1MA3 is derived from a virus called Maraba, which was first isolated from Brazilian sandflies, while AdMA3 is derived from a common cold virus called Adenovirus. Both of these viruses have been engineered to stimulate an immune response against cancer cells that express a protein called MAGE-A3, but the Maraba virus also achieves an extra layer of anti-cancer activity by replicating inside many kinds of cancer cells and killing them directly. These viruses are manufactured in specialized facilities at The Ottawa Hospital and McMaster University.

“The idea behind this trial is to use the Adenovirus to prime the patient’s immune system to recognize their cancer, and then use the Maraba virus to directly kill their cancer and further stimulate their immune system to prevent the cancer coming back,” said Dr. Brian Lichty, associate professor at McMaster University. “We’re enthusiastic about the potential of this unique therapy.”

“We’re very excited about this first clinical trial,” said Dr. Stojdl, senior scientist at the Children’s Hospital of Eastern Ontario and associate professor at the University of Ottawa. “We’re continuing to push very hard to develop a suite of biological therapies with the goal of launching similar trials tailored to other types of tumours, including brain cancer and several devastating childhood cancers.”

Viral therapies are one component of a growing field of cancer research that seeks to use biological materials (including cells, genes, antibodies and viruses) to attack cancer cells and stimulate an anti-cancer immune response. This field of research has been called biotherapy or immunotherapy. Dr. Bell and his colleagues recently launched the$60M BioCanRx network to advance this area of research.

The Maraba virus is an important part of a broad biotherapeutics clinical trial development program in Canada that is combining viruses and vaccines with standard and emerging therapies to treat different types of tumours. Drs. Lichty, Bell and Stojdl and their institutions, in cooperation with the Fight Against Cancer Innovation Trust, have formed Turnstone Biologics in order to engage the private sector and to help fund further clinical trials.

“Immunotherapy is a very exciting field of cancer research, with antibody-based therapies showing the most promise in clinical trials so far,” said Dr. Derek Jonker, the overall lead for the clinical trial, a medical oncologist at The Ottawa Hospital and a professor at the University of Ottawa. “Viral therapies have also shown promise in laboratory studies, but it is too soon to know what impact they may have on patients. This clinical trial will help us find out and we’re very grateful to the patients who have participated.”

“Ontario is pleased to support innovative research through the Ontario Institute for Cancer Research,” said Reza Moridi, Ontario Minister of Research and Innovation. “Our investments have enabled our researchers to be at the forefront of this new therapy. Immunotherapy has the potential to vastly improve the way cancer is treated, and is another example of how research investment brings tangible benefits to Ontarians and people around the world.”

“The NCIC Clinical Trials Group is very pleased to conduct this trial, which offers a potential new therapeutic approach for cancer patients that has been developed by Canadian researchers,” said Dr. Janet Dancey, director, NCIC Clinical Trials Group and professor at Queen’s University in Kingston.

“Our Government is committed to investing in research that will accelerate efforts to find a cure for cancer, a disease that kills thousands of Canadians each year. The clinical trial announced today represents an innovative approach to treating cancer. We are proud to have contributed to the development of this therapy and wish the researchers and clinicians every success as they carry out this important study,” said the Honourable Rona Ambrose, Canada’sMinister of Health.

In addition to The Ottawa Hospital, the clinical trial is also taking place at the Juravinski Cancer Centre of Hamilton Health Sciences (under the leadership of Dr. Sebastien Hotte), Princess Margaret Cancer Centre of the University Health Network in Toronto (under the leadership of Dr. Albiruni R A Razak) and the Vancouver Centre of the BC Cancer Agency (under the leadership of Dr. Daniel Renouf). The trial was approved by Health Canada, the Ontario Cancer Research Ethics Board and the BC Cancer Agency Research Ethics Board. Further details about the trial are available at clinicaltrials.gov. Patients wishing to participate in the trial should speak with their own oncologist and ask for a referral to one of the participating hospitals. Further details for patients at The Ottawa Hospital are available online.

While this trial is primarily funded by the Government of Ontario through the Ontario Institute for Cancer Research, many other funding organizations have also supported the research of Drs. Bell, Lichty and Stojdl, including The Ottawa Hospital Foundation, CHEO Foundation, Canadian Cancer Society, Terry Fox Research Institute, Canadian Institutes of Health Research, Ontario Ministry of Research and Innovation, Canada Foundation for Innovation, Ottawa Regional Cancer Foundation, Hair Donation Ottawa, Angels of Hope, BioCanRx, Pancreatic Cancer Canada, NAV Canada and several philanthropic donors.

About the Partners

The Ottawa Hospital is one of Canada’s largest learning and research hospitals with over 1,100 beds, approximately 12,000 staff and an annual budget of over $1.2 billion. Our focus on research and learning helps us develop new and innovative ways to treat patients and improve care. As a multi-campus hospital, affiliated with the University of Ottawa, we deliver specialized care to the Eastern Ontario region, but our techniques and research discoveries are adopted around the world. We engage the community at all levels to support our vision for better patient care.www.ottawahospital.on.ca

McMaster University, one of four Canadian universities listed among the Top 100 universities in the world, is renowned for its innovation in both learning and discovery. It has a student population of 30,000, and more than 170,000 alumni in 137 countries. Its Michael G. DeGroote School of Medicine has a global reputation for educational advancement and its development of evidence-based medicine. McMaster and its academic hospital partner Hamilton Health Sciences are internationally known for their research intensity.

The CHEO Research Institute coordinates the research activities of the Children’s Hospital ofEastern Ontario (CHEO) and is affiliated with the University of Ottawa. Its three programs of research include molecular biomedicine, health information technology, and evidence to practice research. Key themes include cancer, diabetes, obesity, mental health, emergency medicine, musculoskeletal health, electronic health information and privacy, and genetics of rare disease. The CHEO Research Institute makes discoveries today for healthier kids tomorrow. For more information, visit www.cheori.org

The Ontario Institute for Cancer Research (OICR) is an innovative cancer research and development institute dedicated to prevention, early detection, diagnosis and treatment of cancer. The Institute is an independent, not-for-profit corporation, supported by the Government of Ontario. OICR’s research supports more than 1,700 investigators, clinician scientists, research staff and trainees located at its headquarters and in research institutes and academia across the Province of Ontario. OICR has key research efforts underway in small molecules, biologics, stem cells, imaging, genomics, informatics and bio-computing. For more information, please visit the website at www.oicr.on.ca.

The NCIC CTG is the only Canadian cooperative cancer trials group conducting the entire range of cancer trials from early phase studies to large international randomized controlled trials across all cancer types. Its primary mission is to assess the effectiveness of interventions to prevent the development of cancer or improve the care of those patients who do develop cancer. NCIC CTG trials have led to improved outcomes for cancer patients. It is a national research program of the Canadian Cancer Society. The NCIC CTG’s Central Operations and Statistics Office is located at Queen’s University in Kingston, Ontario, Canada

Read More

China to reform drug approval system

China has decided to reform its appraisal and approval system for drugs and medical instruments with the aim of improving drug safety and quality and encouraging innovation.

According to a guideline issued by the China State Council on Aug. 18, China aims to set up a more scientific and efficient system to ensure the safety and quality of medicines and medical instruments that come into the market.The relevant authorities will make efforts to strike a balance between the number of registration applications received and those that are approved by the end of 2016. They also will ensure that, by 2018, every application will be approved or rejected within a certain time limit.The State Council requested that the approval standards for medicines should be improved by adjusting the classification of drug registration. The appraisal and approval process of innovative drugs will be accelerated, including drugs to treat AIDS, cancer, serious infectious and rare diseases.

Institutions and staff involved in the R&D of drugs will be allowed to apply for the registration of new drugs. Once these drugs are transferred to enterprises for manufacturing, no further appraisal will be required.Approvals concerning the clinical trials of drugs and medical instruments will be further improved. Additionally, procedures on drug approvals will be simplified, so that applications for drugs and relevant packing and materials will be approved at the same time.In order to enhance the transparency of approvals, information concerning drug supply and demand, as well as registration applications, will be released in a timely manner. The public will be able to view the list of approvals and make enquiries, if required, and applicants also will be informed of the approval process and results.

Read More

Universal flu vaccine steps closer

Flu vaccines in the US are made to target a small number of viral strains based on public health experts’ predictions. Scientists hope that, one day, a universal flu vaccine will be developed that will be effective against all strains, and the findings of a new study may take researchers one step closer to this goal.

The study, published in Cell, found that chemical modifications to a specific region in antibodies could be used to improve current flu vaccines.

“We believe these results may represent a preliminary step toward a universal flu vaccine, one that is effective against a broad range of the flu viruses,” states senior author Jeffrey Ravetch, head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology at the Rockefeller University, New York.

Vaccines in the US are typically formulated to target H1 and H3 influenza A viruses along with influenza B strains predicted by experts to be prevalent during the coming flu season. If the experts’ predictions are inaccurate, however, then the vaccines are rendered ineffective.

Just this January, the Centers for Disease Control and Prevention (CDC) reported that this season’s flu vaccine was only 23% effective across all age groups, due to a large proportion of this season’s viruses being “drift variants.”

“While the conventional flu vaccine protects only against specific strains, usually three of them, our experiments show that by including modified antibodies within the vaccine it may be possible to elicit broad protection against many strains simultaneously,” explains Ravetch.

Influenza can be a dangerous illness – particularly in adults over the age of 65 and people with other health conditions. The American Lung Association state that 90% of deaths from influenza occur in adults older than 65.It is a difficult virus for scientists to target with vaccines due to the wide variety of strains that exist, with new strains emerging regularly. Because of how elusive the virus can be, a universal vaccine represents a dream goal for scientists and has been the focus of many research projects.

The new study revolves around a new strategy involving the Fc region of antibodies – the region that connects with immune cells. The researchers, led by Taia Wang and Jad Maamary, already knew that modifying the Fc region affected how the antibodies interacted with immune cells, and so the team set out to investigate how changes to the region might improve an immune response.

Efficacy of improved vaccine: ‘no small accomplishment’

Healthy volunteers were vaccinated with a seasonal flu vaccine containing an inactivated strain of the H1N1 virus – also known as swine flu. Using blood samples, the researchers tracked how the participants’ immune systems responded, looking for chemical modifications to antibodies against a surface protein. Around a week later, the researchers noticed an increase in the number of sialylated antibodies present. Sialic acid is a molecule crucial to signaling, meaning that the presence of these antibodies indicated a positive response to the vaccine.

Experiments on cell cultures and mice revealed that sialylated Fc regions bind to a receptor protein called CD23 on specific immune cells called B cells. In turn, CD23 activates another receptor known as FcyRIIB that discourages B cells from producing low-affinity antibodies.

In short, sialylated Fc regions lead to the activation of B cells producing the highest affinity antibodies. The researchers found that this higher affinity resulted in broad protection against influenza viruses from the H1 subtype (to which H1N1 belongs).

Using this discovery, the researchers modified the H1N1 vaccine by adding sialylated antibodies against the virus’ protein. The new and improved vaccine was then tested on mice.

“When we immunized mice with just the H1 protein from one strain or with the sialylated complexes containing the same viral protein, we found both offered equal protection against the same strain of flu,” explains Maamary. “However, when we exposed them to strains expressing different versions of the H1 protein, only the sialylated immunizations offered protection.”

Wang believes the new mechanism they have uncovered could potentially be utilized to reduce the rates of morbidity and mortality attributable to seasonal influenza virus infections.

“We are now looking into applying this strategy toward improving existing vaccines; ideally, this would result in a vaccine that provides lifelong immunity against flu infections,” she states.

Earlier this year, Medical News Today reported on a study suggesting that a newly discovered class of antibodies could lead to a universal flu vaccine “within 5 years.”

Read More

Cystic fibrosis: yeast study may address root cause

Yast is helping to tackle the root cause of cystic fibrosis – a disease that results from faulty ion channels. A new study shows how a small molecule can take the place of a missing protein in yeast cells with faulty ion channels, enabling them to work again.

The study, by researchers from the University of Illinois at Urbana-Champaign, is published in the Journal of the American Chemical Society.

All organisms – from microbes to humans – rely on protein pumps and channels that transport ions across the cell membrane. Faulty ion channels in cells underlie many currently incurable human diseases.

Cystic fibrosis is caused by a genetic mutation that affects some of the proteins that make up ion channels, causing them to malfunction. The result is a thick build up of mucus in the lungs and other organs, making breathing difficult.

While treatments for cystic fibrosis exist, they do not fix the underlying cause. Treatments include inhalants, enzyme supplements and clearing the airways, which can usually only be done with help.

Yeast is a useful organism for researching human health and disease because yeast cells are very similar to human cells. On two occasions, yeast has featured in studies that have won Nobel prizes (one in 2001, the other in 2009) for their work on human cells.

The new study describes how a small molecule can take the place of a missing protein to restore the type of ion channel function that is missing in people with cystic fibrosis and similar diseases. The molecule – amphotericin B – was originally extracted from bacteria and is used to treat fungal infections.

THE SMALL MOLECULE CAUSED DEFICIENT YEAST TO GROW NEARLY AS WELL AS NORMAL YEAST

The team tested the small molecule at low doses in a strain of yeast that cannot grow because it has faulty ion channels.

Fast facts about cystic fibrosis

• People with cystic fibrosis have inherited two copies of the defective CF gene
• About 70,000 people worldwide are living with cystic fibrosis
• Most cases are diagnosed by the age of 2.

When they added the molecule, the researchers found the yeast grew nearly as well as a normal strain that they used as a control. They note:

“Here we report vigorous and sustainable restoration of yeast cell growth by replacing missing protein ion transporters with imperfect small molecule mimics.”

The authors say more research is needed to confirm whether the small molecule will work in human diseases like cystic fibrosis. In the meantime, however, they conclude that their study provides a “framework for pursuing such a therapeutic strategy.”

People with cystic fibrosis are at greater risk of lung infection because the thick, sticky mucus that builds up in the lungs allows germs to thrive and multiply.

Earlier this year, Medical News Today reported how researchers are reaching a better understanding of infections in cystic fibrosis. A small study of children with the disease reveals that the microorganisms that infect people with cystic fibrosis can survive on little to no oxygen.

Read More

Age-related immune system decline slowed by antioxidants

The thymus is an organ that produces T lymphocytes – white blood cells that are crucial to the immune system.

New research has demonstrated how the aging process damages the immune system, while showing how antioxidants in the diet could slow the build-up of this damage.

Findings from the study, published in Cell Reports, also lend support to the “free-radical theory” of aging, whereby reactive oxygen species such as hydrogen peroxide that are produced by normal metabolism cause damage to cells. This damage contributes to both aging and age-related diseases.

The study was conducted by researchers from The Scripps Research Institute (TSRI) who focused their attention on an organ called the thymus that is responsible for the production of T lymphocytes – also referred to as T cells.

T cells are white blood cells that control the body’s immune response. These cells are continuously lost, and it is the job of the thymus – located between the lungs – to replenish them, enabling the body to respond to new infections. However, the thymus is unable to continuously produce high levels of T cells.

“The thymus begins to atrophy rapidly in very early adulthood, simultaneously losing its function,” explains study author Dr. Howard Petrie. “This new study shows for the first time a mechanism for the long-suspected connection between normal immune function and antioxidants.”

Antioxidants are substances that could prevent or delay damage to cells. Examples include beta-carotene, vitamin C and vitamin E. They can often be found in fruits and vegetables and are also available in the form of supplements.

The researchers set out to explore the mechanisms behind the connection by developing a computational approach they could use to assess gene activity in two types of thymus cell in mice – stromal cells and lymphoid cells.

In the stromal cells, they observed that a deficiency in an antioxidant enzyme called catalase led to the production of reactive oxygen species through metabolism, which in turn sped up the rate at which damage occurred.

COMMON DIETARY ANTIOXIDANTS FOUND TO PRESERVE SIZE OF THE THYMUS

The researchers then tested the role of this antioxidant by increasing catalase levels in genetically altered animal models. By doing this, they were able to maintain the size of the thymus for a longer period.

In addition, the researchers were also able to preserve the size of the thymus in animals by giving them two common dietary antioxidants – including vitamin C.

The question of why the thymus decreases in size more rapidly than other body tissues remains unanswered, however. Dr. Petrie says that while other research has demonstrated the thymus is responsive to sex hormones, their new study shows that its aging process is the same as in other tissues.

“However, the process is accelerated in the thymus by a deficiency in the essential protective effects of catalase, which is found at higher levels in almost all other body tissues,” he continues.

The researchers also point out that while increasing catalase levels in stromal cells preserved the size of the thymus for a longer period, it did not prevent it from atrophying – as yet, there is no way to completely halt metabolic damage accumulated over time.

Read More