A Patient Advocate and Doctor’s Perspective on Clinical Trials: Update on the Retigabine Phase II Trial

Last week, Dr. Brian Wainger of Massachusetts General Hospital and Stephen Winthrop, Chairman of The ALS Association Board of Trustees, gave their unique clinical trial perspectives during the Northeast ALS Consortium (NEALS) webinar titled, “Retigabine Clinical Trial Update & Discussion with ALS Patient Advocate Stephen Winthrop.” For many years, The ALS Association has proudly partnered with NEALS to run ALS centered webinars to disseminate the most up-to-date information to the ALS community. Today’s post discusses the actively enrolling Retigabine clinical trial, which The ALS Association funds, as well as an honest perspective on what it is like to participate in ALS clinical trials.


Patient advocate and a championed NEALS Research Ambassador, Stephen Winthrop (pictured LEFT), joined the discussion to give his thoughtful perspective of clinical trial participation. Stephen was diagnosed with ALS almost four years ago and has been involved in over 12 ALS clinical trials – both observational (does not test a drug) and interventional (tests a drug), including the Retigabine study. The decision to participate in a clinical trial is a complicated question with arguments for and against. Stephen provides honest insights on the pluses and minuses of clinical trial involvement, while giving real life examples of some of his experiences.

“The quality and the experience will vary depending on the test and the individuals you are working with. It is a big question of fit,” Stephen explains.

He goes on to state, “The only way we are going to beat this awful disease is by finding a cure and one small way I can do that is by participating in clinical trials. Yes, it involves a needle stick and yes it takes a little time out of your day, but it is worth it. You are helping.”

Dr. Wainger (pictured RIGHT), one of the Principle Investigators of the Retigabine phase II clinical trial, gave a brief trial overview and update. The Retigabine trial is a double-blinded, placebo-controlled study to test the drug as a potential treatment for people living with ALS. The trial is actively recruiting at 12 sites in the U.S. The primary goals are to measure the effects of Retigabine on upper and lower motor neurons (i.e. the cells that die in ALS) physiology in people with ALS and evaluate safety outcomes.

During the first part of the webinar, Dr. Wainger explains the trial clinical rationale and goes over the study in detail including the goals, inclusion/exclusion criteria, the study timeline and what the study requires from its participants. The goal is to enroll at least 30 more ALS patients into the trial as soon as possible.

Watch the webinar here for all the detailed information.

The trial focuses on hyperexcitability of motor neurons. It was previously shown that people living with ALS have motor neurons (both upper and lower) that fire too many signals, meaning they are hyperexcitable. Too much firing leads to motor neuron damage. Retigabine is designed to reduce the over firing of motor neurons.

To physiologically test motor neuron hyperexcitability in trial participants in real time, the investigators use techniques called transcranial magnetic stimulation (TMS) and nerve conduction studies. These specialized tests are a way to measure the connections between motor neurons and muscles. TMS works by stimulating the motor cortex (part of the brain that controls muscle movement) with a magnet and records the response of the muscles in the hand. Nerve conduction studies evaluate the ability of motor neurons to conduct signals to muscles. An important secondary outcome of this study is to determine the potential for the use of these techniques for future ALS trials.

Stephen explains, “What they were trying to do using TMS, which looks like a ping pong paddle held above my head, was to try to make my right thumb to twitch by increasing the magnetic field. No pain was involved to see if my thumb twitched or did not twitch.”

One unique aspect of the Retigabine clinical trial to highlight is that each trial participant will donate a blood sample to be made into induced pluripotent stem cells (iPSCs). These iPSCs are then made into motor neurons in a dish, which reflect the exact genetic makeup of the person they were derived from.

The effects of Retigabine on patient derived motor neurons will also be tracked and compared to the impact of the drug on the patient. This is the first ALS clinical trial to attempt this type of comparison, which has potential as a prognostic and diagnostic tool. Patient derived iPSCs could even possibly predict how a subgroup of ALS patients respond to a drug, which would improve clinical trial design and recruitment.

Stephen adds, “There are so many aspects of this study that is adding to the knowledge base that Brian and his colleagues around the country and around the world are using that plant seeds for clinical successes in the future.”

“One of the things I have said about participating in a clinical trial is that when you are in a room with someone with ALS, do not forget about the human dimension of what you are looking at here. Don’t forget to say to a potential participant, ‘I am sorry that you have been struck by this awful disease,’ and just let that pause. Don’t forget to say, ‘Thank you or thanks for your small part.’”

“In my own experience, those seemingly routine personal touches go a long way, because in the end I do think their decision to participate is fueled in part by just a little whisper of a hope that this will maybe help me. The bigger piece is that you, as a participant, are part of an army of people – I truly believe – will bring an end to this disease.”

We are thankful to Stephen for giving his honest perspectives and we value his dedication to the fight against ALS. With passionate, committed physicians, researchers, clinic staff, allied professionals and especially clinical trial participants – both living with ALS and healthy – all working together in clinical trials, we are many steps closer to a cure.

Watch the full webinar here.

For more information about the Retigabine trial visit the NEALS trial siteand clinicaltrials.gov #NCT02450552.

Revolutionary Study Identifies New Genes Involved in ALS

Barrow Neurological Institute and IBM Watson Health today announced results of a revolutionary study that has identified new genes linked to amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. The discovery gives ALS researchers new insights that will pave the way for the development of new drug targets and therapies to combat one of the world’s most devastating and deadly diseases.

The groundbreaking discovery involved IBM Watson, a cutting-edge form of artificial intelligence, to help unravel the mysteries of the brain and provide Barrow scientists with never-before-known data. IBM Watson became known around the nation in 2011 when it competed against human contestants on Jeopardy, and won. Continue reading Revolutionary Study Identifies New Genes Involved in ALS

New Disease Mechanism Revealed for C9orf72 Gene Mutations

research news banner 2015In a new study funded by The ALS Association, Yong-Jie Zhang, Ph.D., Leonard Petrucelli, Ph.D., and their research team from the Mayo Clinic in Jacksonville, Fla. have uncovered a new and potentially important disease mechanism that occurs in the C9orf72 gene, the most common genetic form of ALS. This study was published today in top-tiered scientific journal Nature Neuroscience.

Continue reading New Disease Mechanism Revealed for C9orf72 Gene Mutations

New Discovery of Normal Function of ALS Gene Will Aid Drug Development to Slow or Stop Disease

ALS research news banner 2015Mutations in the C9orf72 gene are known to be the most common genetic cause of ALS. According to new research, C9orf72 is important for immune system function in its normal form, an important discovery made by scientists Jacqueline O’Rourke, Ph.D., and Robert Baloh, M.D., of Cedars-Sinai Medical Center in Los Angeles, that is likely to influence the development of treatments aimed at silencing the C9orf72 mutant gene. The findings were published today in the journal Science.

Continue reading New Discovery of Normal Function of ALS Gene Will Aid Drug Development to Slow or Stop Disease

Spotlight on Dr. Javier Jara, A 2010 Safenowitz Fellow

ALS Researcher Javier Jara, Ph.D.

“Our ability to make progress in ALS depends so much on attracting the best young scientists into the field. The ALS Association’s Milton Safenowitz Post-Doctoral Fellowship program is a critical part of that effort. Almost 90 percent of our Fellows stay in ALS research, making up a significant fraction of the younger generation of ALS researchers.”
– Dr. Lucie Bruijn, Ph.D., M.B.A., Chief Scientist, The ALS Association

The Milton Safenowitz Post-Doctoral Fellowship for ALS Research Award is designed to encourage and facilitate promising young scientists to enter the ALS field. The award program was founded by the Safenowitz family, through the Greater New York Chapter of The ALS Association, and awards are given in memory of Mr. Safenowitz. Fellows work with a senior mentor and receive extensive exposure to the ALS research community through meetings and presentations. More than 90 percent of Milton Safenowitz fellows remain in ALS Research and contribute significantly to the advances made in the field.

Javier Jara, Ph.D., is a Research Assistant Professor in Dr. Hande Ozdinler’s laboratory in the Department of Neurology at the Northwestern University Feinberg School of Medicine in Chicago. He was funded by The ALS Association’s Milton Safenowitz Post-Doctoral Fellowship for ALS Research from 2010-2012 and recently was awarded his own Investigator-Initiated grant by The Association.

The award helped support Dr. Jara research including a project that focuses on how upper motor neurons die in ALS and how to intervene to prevent their death. The results of this project were featured in the January 21, 2016, issue of Gene Therapy. Recently, we sat down with Dr. Jara to learn more about his exciting research project and to get to know the person behind the science.

Continue reading Spotlight on Dr. Javier Jara, A 2010 Safenowitz Fellow

The ALS Association Invests More Than $1.9 Million to Discover Treatments for ALS

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The ALS Association is pleased to announce five new Translational Research Advancing Therapy for ALS (TREAT ALS™) grant recipients to fund milestone driven amyotrophic lateral sclerosis (ALS) research. The TREAT ALS™ portfolio is a diverse collection of ALS research to find treatments and a cure for ALS. These awards include a TREAT ALS™ Drug Development Contract grant and ALS Association-Initiated grants totaling $1,950,340.

Continue reading The ALS Association Invests More Than $1.9 Million to Discover Treatments for ALS

The ALS Association Funds Five New Grants in the TREAT ALS™ Porfolio

March 2016

TREAT ALS™ Drug Development Contracts

Drug development contracts are milestone-driven awards designed to rapidly bring the most promising potential therapies closer to clinical trials. Many of the contracts are in partnership with industry. Academic-industry partnerships are invaluable to drive treatment approaches for ALS more rapidly to the clinic.

Continue reading The ALS Association Funds Five New Grants in the TREAT ALS™ Porfolio

Long Island PALS Accepted as Research Ambassador at Annual NEALS Conference

2015 CRLI

As a retired optometrist from Long Island, Frank Verdone has a clear understanding of the science behind clinical trials that may help to find a cure for ALS. As a person living with ALS, the 55-year old former long distance runner has enthusiastically volunteered to be trained as a NEALS Research Ambassador to educate others about the latest ALS clinical trials and inspire PALS to participate in them.

When Theresa Imperato, RN, Nurse Coordinator at the ALSA Certified Center at Stony Brook University Hospital, got an announcement that NEALS was seeking Research Ambassadors, she thought of Frank because of his medical background and interest in current research. “He wants to find a cure if not for himself but also for those diagnosed in the near future,” Theresa said. Frank has also participated in ALS studies so he has first-hand experience with clinical research.

As a result, Frank was accepted into the program and attended the 14th Annual NEALS Consortium Conference last November. The ALS Clinical Research Learning Institute, sponsored by the ALS Association’s TREAT ALS initiative, is an intensive two day program dedicated to educating attendees on clinical research and therapy development and empowering them to be advocates for ALS clinical research. ALS Association Chief Scientist Dr. Lucie Bruijn was also in attendance. “We brought this information back to our support groups to explain why clinical trials are so necessary and to try to get patients involved,” said Frank, who was one of 34 Research Ambassadors from all over the country including one couple from Canada and one from Puerto Rico. Of those, 15 were PALS who take on the role permanently.

Frank’s wife, Mary, accompanied him to the NEALS meeting where she learned how much work is being done in the field, how compassionate the researchers are, and that there is hope for an effective treatment in the near future. Frank noted that meeting other patients and caregivers was a comfort to them; to know that they were not alone in the fight for a cure.

Frank is a dedicated advocate for the Greater New York Chapter and a natural fit as Ambassador because he finds inspiration in educating people about ALS. He often visits local school districts to talk about ALS and the story of Lou Gehrig. “These are life lessons for all children at any age,” Frank said. “After our presentation, principals and teachers always comment on how this is the best presentation they have ever heard and students are compelled to run fundraisers for our cause afterwards.”

In addition to advocacy work, Frank keeps very busy. He attends the Chapter’s monthly support group and ALS clinic at Stony Brook University Hospital. “I find the support groups to be a wealth of information,” he said. “And all of the medical providers and staff at the clinic provide us with the best care.” Frank serves on the board of Long Island based Ride For Life. He and his family started Team FrankV in his honor to raise awareness and funds for the Long Island Walk to Defeat ALS.

For more information about becoming an ALS advocate please contact Jeanne Traugot, Director of Development, at (212) 720-3051 or jtraugot@als-ny.org.

New Evidence Supports Nuclear Transport Disruption as a Key ALS Pathway

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Researchers from the Max Planck Institute of Biochemistry in Martinsried, Germany demonstrated that protein aggregates, like those found in the neurons of most people with ALS, are toxic when they occur in a cell’s cytoplasm, not its nucleus. The study was published in the Jan. 8, 2016 issue of the journal Science titled, “Cytoplasmic protein aggregates interfere with nucleocytoplasmic transport of protein and RNA.” These cytoplasmic aggregates interrupted transport of materials to and from the nucleus. The findings add to earlier publications highlighting the potential of disrupted nuclear transport as a disease pathway in ALS and may lead to better targeting of therapy.

In the study, researchers introduced artificial proteins that carried localization sequences, akin to zip codes, that restricted them to either the cell’s nucleus or its surrounding cytoplasm. The proteins were designed to form aggregates, clumps of protein that are thought to interfere with cell function. Protein aggregates are a common feature in numerous neurodegenerative diseases, including ALS, Alzheimer’s disease, Parkinson’s disease, among others. The researchers found that only the cytoplasmic aggregates were toxic.

The team also found that cytoplasmic aggregates disrupted transport of materials across the nuclear membrane. Disrupted nuclear transport has recently emerged as a potentially major disease pathway in ALS, following work by ALS Association-funded researchers.

“The results in this study strengthen the case that interference with nuclear transport is a key element of the disease process in ALS,” said Association Chief Scientist Lucie Bruijn, Ph.D., M.B.A. “Treatments that are aimed at preventing or reducing cytoplasmic aggregation of ALS-related proteins, including TDP-43, will be important to explore for their potential in ALS.”

Neuro Collaborative Partner Gladstone Institutes Forms New Collaboration with Biogen In ALS Research

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The ALS Association is pleased to announce a new collaboration between the Gladstone Institutes in San Francisco, which is a member of The Association-funded Neuro Collaborative and the biotechnology company Biogen in Cambridge, Mass., to discover novel drug targets for the treatment of amyotrophic lateral sclerosis (ALS).

The Neuro Collaborative is an innovative partnership among three California research labs focused on development of new ALS therapies: The Svendsen lab at Cedars-Sinai in Los Angeles, site of the groups’ stem cell core; the Cleveland lab at the University of California San Diego, engaged in development of novel therapeutics; and the Finkbeiner lab at the Gladstone Institutes, which is affiliated with the University of California at San Francisco.

The Neuro Collaborative is funded by The ALS Association with a $5 million grant stemming from the funds raised through the Ice Bucket Challenge. Part of the Neuro Collaborative’s mission is to develop potential therapies that can be delivered to pharmaceutical companies for clinical trials.

Gladstone Senior Investigator Steven Finkbeiner, MD, Ph.D. and his group, invented and use a novel robotic microscopy system, called “Brain Bot,” which allows longitudinal imaging of individual neurons in culture, making target identification and drug discovery faster and more efficient. The lab has identified protein homeostasis as an important factor underlying neurodegeneration. To this end, they are leveraging their microscopy system to develop novel small molecule therapeutics that can clear toxic proteins from neurons and extend their lifespan. In addition, the lab is carrying out screens in search of novel drug targets that could be used to design new therapeutics that mitigate neurodegeneration.

Biogen has carried out genetic screens for genes that affect Drosophila ALS models and identified numerous potential targets that improve ALS-related phenotypes in these models. To evaluate and further validate potential targets for the development of new medicines, Biogen is interested in carrying out secondary screens in mammalian neurons. The new collaboration between the Finkbeiner lab and Biogen will greatly accelerate this effort.

“We are deeply gratified to see the emergence of this new collaboration,” said Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The ALS Association. “We believe the fastest route to new therapies for ALS is through forging partnerships such as this one, which combines the expertise of a major research laboratory with that of a major biotechnology company, both of which have proven their ability and commitment to advancing the discovery of new ALS treatments.”

“This collaboration offers us the opportunity to bring our state-of-the-art imaging technology fully to bear on the critical challenge for discovery of new ALS drug targets,” Dr. Finkbeiner said.

ALS is a significant focus of drug discovery and development at Biogen, a research-driven biotechnology company that has developed multiple medicines for neurologic conditions. This collaboration is expected to lead to better understanding of disease mechanisms, identification of new drug targets, and accelerate development of new treatments for ALS.

“Biogen is committed to ALS research and collaborating with the world’s best scientists to tackle this devastating disease,” said Spyros Artavanis-Tsakonas, Ph.D., Chief Scientific Officer at Biogen. “We are excited to combine our capabilities in pathway discovery and target validation with the screening technologies and imaging expertise of the Gladstone Institutes’ Neuro Collaborative to find new answers to ALS.”

The Gladstone-Biogen collaboration is scheduled to start in the first quarter of 2016 and will be led by Dr. Finkbeiner and Dr. Ashkan Javaherian at the Gladstone Institutes along with Dr. Mark Kankel and Dr. Anindya Sen from the Pathway Discovery research group at Biogen. The collaboration will include developing novel cellular models of ALS and building an infrastructure for high-throughput screening to identify new drug targets and develop small molecule therapeutics for ALS.

About ALS
ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which often leads to total paralysis and death within two to five years of diagnosis. For unknown reasons, veterans are twice as likely to develop ALS as the general population. There is no cure, and only one drug approved by the U.S. Food and Drug Administration (FDA) modestly extends survival.

About the Gladstone Institutes
To ensure our work does the greatest good, the Gladstone Institutes focuses on conditions with profound medical, economic, and social impact—unsolved diseases of the brain, the heart, and the immune system. Affiliated with the University of California, San Francisco, Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. Find more information at gladstone.org.

About Biogen
Through cutting-edge science and medicine, Biogen discovers, develops and delivers to patients worldwide innovative therapies for the treatment of neurodegenerative diseases, hematologic conditions and autoimmune disorders. Founded in 1978, Biogen is one of the world’s oldest independent biotechnology companies and patients worldwide benefit from its leading multiple sclerosis and innovative hemophilia therapies. For product labeling, press releases and additional information about the company, please visit www.biogen.com.