The ALS Association

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Carrie Munk
The ALS Association
(571) 319-3047



Rapid Therapy Development was the Focus of Recent Research Meeting

Washington, D.C. (October 14, 2015) — The ALS Association’s singular focus on development of new treatments for ALS took center stage at the recent three-day research conference, held at the Banbury Center at Cold Spring Harbor Laboratory in Huntington, New York and generously sponsored by The Greater New York Chapter of The ALS Association. The meeting brought together the leaders in research development in three of the most promising therapeutic areas: antisense oligonucleotides, gene therapy, and stem cell therapy, as well as leading researchers in the related fields of trial development, model systems, and biomarker discovery.

ALS Researchers gathered for a three-day conference at the Banbury Center at Cold Spring Harbor Laboratory in Huntington, New York.

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.

“Our purpose in holding these small scientific meetings is to encourage key researchers to engage in a free flow of dialogue that can bring out important ideas, point out weaknesses in approach that need strengthening, and promote collaboration to push the field forward,” said Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The ALS Association. “Judged by those criteria, the meeting was a terrific success.”

Development of therapy for ALS has been directed along two major lines in recent years. Most treatments aim to interrupt or reverse some intermediate step in the disease process, such as inflammation, excitotoxicity, or failure of energy production. It has been hoped that these treatment approaches would be beneficial to most or all people with ALS, whatever the initial cause of their disease. Unfortunately, with the exception or riluzole, the therapies developed to date have not been successful.

More recently, treatments have been developed that aim at the earliest possible step in the disease, by shutting down production from a disease-causing gene. These approaches are necessarily only for those whose ALS is due to a gene mutation. But researchers believe that success in treating one or more genetic forms of ALS will reveal important lessons about the ALS disease process that will help in therapy development for other forms of ALS as well.

Progress in Antisense Therapy
Researchers have made major strides in development of antisense therapy against the two most common genetic causes of ALS: mutations in the SOD1 gene and in the C9orf72 gene. Antisense therapy delivers a molecule that binds to the RNA “working copy” of the mutant gene, triggering its breakdown by cellular machinery and preventing it from promoting other disease-related processes such as inflammation. Antisense treatment against SOD1, delivered by injection into the space surrounding the spinal cord, has been shown to be safe in people with ALS. A clinical trial to test its efficacy is being moved forward, according to lead researcher Timothy Miller, M.D., Ph.D., of the University of Washington in Saint Louis.

An antisense trial against the C9orf72 mutation is also in development and is expected to begin in late 2016. Don Cleveland, Ph.D., of the University of California at San Diego, reported that results from cell and animal models support going forward with a safety trial. Antisense therapy has been shown to be safe in another motor neuron disease, spinal muscular atrophy. Dr. Cleveland also described a new therapeutic system based on a recently developed system of “gene editing” called CRISPR that his lab is developing to determine its therapeutic potential for ALS.

Gene Therapy
Several researchers described their work in developing gene therapy approaches to ALS. In gene therapy, a gene is introduced into the nervous system that enters cells and is then expressed (that is, churns out RNA working copies). The delivered gene might be one that creates an antisense molecule, or a growth factor, or some other potentially therapeutic substance. A potential advantage for gene therapy over direct delivery of an antisense molecule is that the gene is expressed for long periods of time, perhaps as long as five years or more. While it is not known how long directly delivered antisense molecules continue to function in humans, it is likely to be months rather than years.

Dinah Sah, Ph.D., of Voyager Therapeutics in Cambridge, Massachusetts, explained her company’s development of a gene that targets SOD1, which is delivered by the adeno-associated virus vector (AAV). AAV has emerged as one of the safest and most versatile gene carriers (vectors) for use in the central nervous system. The gene creates a “small interfering RNA,” or siRNA, that, like antisense, triggers the breakdown of the SOD1 working copy. Voyager’s work is currently in animal models, with plans to move to human trials in the future.

Brian Kaspar, Ph.D., of Ohio State University, provided some inspiring preliminary results from an AAV trial in spinal muscular atrophy. The most severe form of SMA affects infants, who are unable to make a protein called SMN, critical for survival of motor neurons. In the trial, Dr. Kaspar and colleagues delivered the SMN gene by AAV. The treatment appears to be safe and well tolerated and, at least from early measurements, may be helping to slow the progress of the disease. If further testing supports these results, this will be an important proof of principle that a motor neuron disease can be slowed using a gene therapy approach.

Stem Cell Therapy
A trial of stem cell therapy in ALS is underway and an update was provided by Jonathan Glass, M.D., of Emory University, one of the leaders of the study. In the trial, stem cells were implanted into the spinal cord. The goal, Dr. Glass said, was not to have the cells become motor neurons themselves—it is considered unlikely that transplanted cells could grow out to innervate muscles that have weakened due to loss of the motor neurons that originally controlled them. Instead, the hope is that the transplanted cells will release growth factors to improve the health of remaining motor neurons. So far, the procedure has proved to be safe and the cells have remained alive, according to autopsy studies. The transplant has not led to a measurable change in disease progression, although the trial is ongoing.

Clive Svendsen, Ph.D., of Cedars-Sinai Hospital in Los Angeles, described progress on an alternative stem cell approach. Dr. Svendsen and colleagues have engineered stem cells (more precisely, neural progenitor cells) to release excess growth factors designed to help motor neurons overcome the toxic effects of the ALS disease process. An initial safety trial is likely to commence early in 2016. In the trial, 18 people with ALS will receive injections of stem cells into one side of the lower spinal cord. Disease progression in the legs will be monitored, and compared side to side, based on the understanding that, in the absence of therapy, progression should be the same on both sides.

Other Topics and Key Discussions
Effective clinical trials require robust biomarkers to show whether and where a drug, or a cell, is having an effect. Meeting participants reviewed progress in development of several kinds of biomarkers, including imaging markers for transplanted cells. Any therapy that proves itself in early trials will need to be manufactured in large quantities for larger trials and ultimately treatment of many people with ALS. The many challenges to ramping up production of such unique therapeutics as stem cells and AAV vectors were discussed at length. New animal models of the C9orf72 gene have been highly challenging to create but are now being developed and used for initial exploration of the gene’s effects in rodents, rather than cell lines.

Among the most exciting topics presented was the SOD1 dog model of ALS, described by Joan Coates, D.V.M., of the University of Missouri. Mutations in the SOD1 gene occur naturally in a large minority of dogs, and are one of the leading causes of late-onset hindlimb weakness (the disease is called canine degenerative myelopathy). Dr. Coates has developed a large program of study of the dogs, including developing a detailed understanding of the genetics, pathophysiology, and preclinical therapeutic potential in the model, in partnerships with Dr. Miller and others. Much remains to be accomplished, including a search for genetic modifiers of onset and severity, biomarkers that may parallel those under development in ALS, and developing the infrastructure for testing therapies such as antisense.

“The excitement among our researchers about the progress of therapy for ALS is what drives the field forward,” Dr. Bruijn commented. “We saw at this meeting, as we see every day, their commitment to finding the most effective treatments in the shortest possible time frame. We are all encouraged by the advances being made in the field, and know that we must continue to work even harder to move them forward even faster.”

View the research meeting agenda.

About The ALS Association
The ALS Association is the only national non-profit organization fighting Lou Gehrig’s Disease on every front. By leading the way in global research, providing assistance for people with ALS through a nationwide network of chapters, coordinating multidisciplinary care through certified clinical care centers, and fostering government partnerships, The Association builds hope and enhances quality of life while aggressively searching for new treatments and a cure. For more information about The ALS Association, visit our website at

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