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.

Senate Passes 21st Century Cures Act, December 7th

Senate Passes 21st Century Cures Act

Yesterday, the Senate passed the 21st Century Cures Act, sending the groundbreaking legislation to President Obama’s desk for a signature. The new law will provide billions of dollars to help accelerate the discovery, development, and delivery of promising new treatments by funding research and streamlining the drug review process. Importantly, the bill also will help preserve access to complex rehab technologies (CRT) power wheelchair accessories.

The 21st Century Cures Act is groundbreaking legislation that has taken over two years of negotiations. Thank you to all of the ALS Advocates who wrote letters, made phone calls and spoke to legislators about the legislation. Because of your hard work, ALS Association priorities were included in the final legislation. Continue reading Senate Passes 21st Century Cures Act, December 7th

The ALS Association and Prize4Life Announce Five Finalists for $400K Assistive Technology Challenge


November 22, 2016
The ALS Association and Prize4Life announced today the five finalists for the ALS Assistive Technology Challenge, a $400,000 award for the development of flexible, accessible technology to help people with ALS communicate with ease. The winner of the challenge will be selected in Dublin, Ireland, on Monday, Dec. 5 at the International Symposium of ALS/MND.

“Each one of the five finalist groups took a unique approach for tackling the challenges facing people living with ALS. We are very excited about these innovative and groundbreaking technologies and are confident that any one of them has the potential to make a significant impact on the quality of live of people living with ALS and their families and caregivers,” said Maya Bronfeld, Ph.D., Prize4Life Scientific Officer. Continue reading The ALS Association and Prize4Life Announce Five Finalists for $400K Assistive Technology Challenge

ALS Gene C9orf72 Study Published in Journal “Neuron”

Pictured above: Dr. Gao’s laboratory team

A new disease pathway for C9orf72-related ALS was revealed in journal Neuron in a study led by principle investigator Dr. Fen-Biao Gao from the University of Massachusetts Medical School in Worcester, Mass. The research team found that the C9orf72 expansion leads to DNA damage, signifying another potential ALS therapeutic target. The ALS Association supported this encouraging study that also included current and past Milton Safenowitz Postdoctoral Fellows Dr. Dejun Yang (2015 recipient) and Dr. Helene Tran (2012 recipient).

Continue reading ALS Gene C9orf72 Study Published in Journal “Neuron”

ALS Gene C9orf72 Damages DNA Revealing a New Disease Pathway

The most commonly inherited gene in familial ALS, C9orf72, points to DNA damage causing oxidative stress, according to a new study funded by The ALS Association. The study was published in the journal Neuron and led by principle investigator Fen-Biao Gao, Ph.D. and first author Rodrigo Lopez-Gonzalez, Ph.D. from the Department of Neurology at University of Massachusetts Medical School in Worcester, Mass. Findings from this paper point to DNA damage as a disease pathway of C9orf72-related ALS.

Continue reading ALS Gene C9orf72 Damages DNA Revealing a New Disease Pathway

New Protein Target Emerges for C9orf72 the Most Common Genetic Form of ALS

research news banner 2015Targeting a single protein, called SUPT4H1, reduces the levels of the three toxic entities created by the C9orf72 gene expansion, the most common genetic cause of ALS, according to a study published in the journal Science. The finding suggests that SUPT4H1 may be a promising candidate for therapy development for people whose disease is caused by expansion of the C9orf72 gene. The study was supported by The ALS Association and led by senior investigators Leonard Petrucelli, Ph.D., of the Mayo Clinic in Jacksonville, Fla and Aaron Gitler, Ph.D., of Stanford University in Stanford, Calif., along with co-lead investigators Nicholas Kramer, Ph.D., Yari Carlomagno, Ph.D., Fen-Biao Gao, Ph.D., and Yong-Jie Zhang, Ph.D.

Continue reading New Protein Target Emerges for C9orf72 the Most Common Genetic Form of ALS

Hear ALS Association Chief Scientist Lucie Bruijn, PhD, MBA Speak About ALS Research

Towards therapies for ALS: How ALS Association funded research can impact progress

Tuesday, June 28, 2016 | 6:30 p.m. – 8:30 p.m.
The New York Genome Center,
101 Avenue of the Americas, (bet. Grand & Watts Streets), NYC

Register Here

Meet the speaker, networking and refreshments to follow.

Bio: Lucie Bruijn, PhD, joined The ALS Association in January 2001 and is currently the Chief Scientist. Prior to that Dr. Bruijn led a team at Bristol Myers Squibb developing in vitro and in vivo model systems for neurodegenerative disease. Read more.

Talk Abstract: Over the past several years thanks to increased investment and advances in technology, gene discovery for ALS has grown exponentially and with this the opportunities to develop therapies for this devastating disease. Read more.

The Evening Talks Series is sponsored by The Pyewacket Fund of the New York Community Trust.

New C9orf72 Mouse Models Show Neurodegeneration from Most Common Genetic Cause of ALS

research news banner 2015Two independent research studies both funded by The ALS Association, including principal investigator Laura Ranum, Ph.D., of the University of Florida in Gainesville and the other study led by Don Cleveland, Ph.D., of University of California San Diego in San Diego and Clotilde Lagier-Tourenne, M.D., Ph.D., of Massachusetts General Hospital in Boston, have developed new mouse models of the C9orf72 mutation that show neurodegeneration and motor and cognitive deficits reminiscent of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In addition, one group showed that these effects could be ameliorated in mice by antisense therapy against the mutant gene.

“These studies represent significant progress in understanding the consequences of the C9orf72 gene mutation and in developing a therapy against it,” said Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The ALS Association.

Continue reading New C9orf72 Mouse Models Show Neurodegeneration from Most Common Genetic Cause of ALS

Innovative ALS Imaging Biomarkers Come Closer to Patients

research news banner 2015The Neurological Clinical Research Institute (NCRI) imaging team at MGH, led by Dr. Nazem Atassi, used PET imaging to successfully scan the first person living with ALS to measure inflammation in the brain, a promising first step in this imaging biomarker study. The ALS Association together with The ALS Finding A Cure (ALSFAC) Foundation, a program of the Leandro P. Rizzuto Foundation, funded investigators at Massachusetts General Hospital (MGH), Houston Methodist Hospital and GE Healthcare to develop biomarkers that would help with diagnosis of ALS and measuring the progression of the disease. The goal is to develop novel MRI and positron emission tomography (PET) imaging tools.

Continue reading Innovative ALS Imaging Biomarkers Come Closer to Patients

New ALS Model Argues for Early Treatment

ALS Research BannerWashington, D.C. (December 2, 2015) — Results from two independent research groups on an important new mouse model of inherited ALS gene C9orf72 indicate that development of disease pathology precedes neurodegeneration, and can be reversed by therapies targeting the mutant gene responsible for the pathology. The studies were funded in part by The ALS Association.

Continue reading New ALS Model Argues for Early Treatment