The ALS Association

ALS Ice Bucket Challenge Progress

Government Partnerships and Stem Cell Research Provide the Roadmap to a Cure

June 1, 2008

Leading scientists and government officials addressed a packed room at the Science Update and Stem Cell Update sessions held during The ALS Association’s 2009 National ALS Advocacy Day and Public Policy Conference, which took place in Washington, D.C., May 10-12. The speakers delivered the latest exciting information about the state of ALS research, educating attendees about new strategies for developing treatments and providing new reasons for hope in the fight against ALS.

Importantly, the morning session focused on research made possible by The ALS Association’s advocacy and by the efforts of people with ALS and their families who have reached out to their elected officials during Advocacy Day to generate millions of dollars in federal funding for ALS research.  This outreach has helped to increase funding for ALS research at the National Institutes of Health, the single largest source of ALS research funding in the world.  It also has led to the establishment of two new ALS specific research programs, including the ALS Research Program (ALSRP) at the Department of Defense and the national ALS patient registry at the Centers for Disease Control and Prevention. Through advocacy, these partnerships with the government are creating the roadmap that will lead to a treatment and cure.  A second session focusing on stem cells highlighted the changes in policy with the new administration and the exciting advances in the field.

Addressing the audience of patients, families, and advocates, Lucie Bruijn, Ph.D., senior vice president of research and development at The ALS Association, said “The Association believes strongly that the key to making a difference in ALS is collaboration—among academic researchers, industry, government, funding organizations, Association chapters, clinics, and individuals. You will hear from this panel about the impact you all make.”

Partnerships with NIH, CDC and Department of Defense

A partnership with the National Institute of Neurologic Diseases and Stroke (NINDS) is leading to a trial of lithium in ALS, based on preliminary but promising results from a small trial in Italy. Deputy Director of NINDS, David Koroshetz, M.D., said that moving forward with the lithium trial “is probably the fastest thing we ever did in the history of the Institute.” The usual application procedures were short-circuited, he said, to allocate more than a million dollars to the new trial.

Along with The Association and the National Institutes of Health’s (NIH) Office of Rare Disorders, NINDS recently co-sponsored a workshop on “translational” research, which is designed to translate advances in basic science into new treatments.  NINDS also has funded and supported ALS drug screening efforts to further expedite the search for a treatment.

The NIH, which includes NINDS, “is the taxpayers’ investment in finding new treatments for disease,” Dr. Koroshetz said. The NIH spends $31 billion annually on research, including both basic research and clinical trials. Basic research—discovering how cells work—is vital, he said. “If you are going to try to solve a problem, you can hope to get lucky, or you can try to find out as much as you can about how a cell works.” He pointed out that the foundation for a recent discovery directly relevant to ALS began in basic research on understanding how cells process their genetic messages. The most recent gene linked to ALS is better known to cancer researchers, and early work on the gene was provided by the National Cancer Institute, also part of the NIH.

David Williamson, Ph.D., Director of Health Studies at the Agency for Toxic Substances and Disease Registry, a division of the Centers for Disease Control and Prevention, provided attendees the latest information about the establishment of a national ALS patient registry.  He noted that pilot projects are underway to determine the most effective and efficient ways to identify and verify ALS cases and to share information.  According to Dr. Williamson, the projects are expected to conclude later this year and will help to guide the continuing development of the registry.  Dr. Williamson also shared that the Agency is planning to develop a web-based self-registration tool to enable patients to self-enroll in the registry, a vital way to collect information about ALS cases.

The ALS Association is the leading organization championing the creation of the registry, having partnered with Congress to enact the ALS Registry Act, signed into law in 2008, which authorizes the CDC and ATSDR to implement the registry.  The Association also has worked with Congress to secure nearly $10 million in funding to advance the pilot projects and the broader registry.  In fact, Dr. Williamson noted that “The ALS Association deserves a lot of credit” for getting the registry funded.  Williamson also underscored that the registry is not simply a database of names when he emphasized that the registry will be a vital research tool.  By collecting data on ALS patients from across the country, such as age, geographic location, possible toxic exposures, and work history, the registry can yield important clues about the causes of ALS and how it can be treated or even prevented.

The ALS Association continues to work with Dr. Williamson and his colleagues to advance the registry and will provide the ALS community with updates on new developments as the ATSDR makes progress in creating and implementing this vital research program, which may become the largest single ALS research program ever created.

The Association’s advocacy also has led to the establishment of the ALS Research Program at the Department of Defense (DOD). The program, which is the only ALS specific program at DOD, is specifically designed to promote translational research, with the goal of finding new treatments for ALS.  Ole Isacson, M.D., of Harvard Medical School, provided an update on his research efforts which have been funded by the ALSRP.  Dr. Isacson reported that one project in his lab is to study motor neurons that control the eye muscles. These neurons remain functional long after others have succumbed to the ALS disease process. “By studying the winners, we may learn how to help the others,” he said. “Perhaps we will be able to invent a drug that drives other motor neurons to behave more like those more resilient cells.” His strategy is to look at what genes each type of cell is using to control its functions (while all cells contain the same set of genes, different cells turn on different sets of genes). He has found a gene that is more active in the healthy cells, called IGF2 (insulin-like growth factor 2). He is currently searching for drugs that will increase the amount of IGF2 that other cells will make and possibly change the progression of ALS.

Developments in Stem Cells

Attendees of the Stem Cell Update session heard the latest news about this promising field directly from experts conducting the research. As a member of the Coalition for the Advancement Medical Research, The ALS Association has worked with Congress and the Administration to ensure that we leave no stone unturned in the search for a treatment for ALS, including pursuing stem cell research.   New developments in stem cells have provided hope for speeding ALS research. Not only has the new Administration lifted restrictions on stem cell research, but scientists have learned how to turn a patient’s own cells into stem cells that can then grow, develop, and multiply in a dish, with the potential to mimic the disease process much more closely than is possible in animal models. “These cells are going to change things,” Dr. Bruijn said. “I think we should be very hopeful.”

Clive Svendsen, Ph.D., of the University of Wisconsin, explained why this new technique offers such promise. “Many diseases of the brain don't occur naturally in other animals. Mice are not men,” he said, and therefore the disease process, even in mice induced to develop the disease, is not the same.

The new approach uses a small set of genes to turn adult skin cells back into stem cells (technically called “induced pluripotent stem cells,” or IPS cells). IPS cells have the ability to develop into many other kinds of cells, including motor neurons, the cells that die in ALS. They also die in a related disease of children, called spinal muscular atrophy (SMA). Last year, Dr. Svendsen and colleagues showed that skin cells from an SMA patient could be turned into IPS cells. These could then be turned into motor neurons, which, just like the patient’s own cells, were at greater risk of dying. “The disease can now be replayed over and over in a dish,” Dr. Svendsen said. “In this way, we'll start understanding more about the disease.” Similar work is underway to make ALS-specific cells that also die off. The cells should be useful to identify drugs that protect the cells from the ALS disease process, something that is potentially much faster to do in cells than in animals.

Dr. Svendsen is also developing a treatment approach for ALS. His group is applying for permission to implant patients with cells called astrocytes that make a growth factor, called glial derived neurotrophic factor or GDNF, which helps protect motor neurons. The application process is slow, he said, “but it’s important to get the treatment right the first time. Getting it wrong could set the whole field back many years.”

The audience also heard from Karl Johe, Ph.D., of the biotechnology firm Neuralstem, which is developing cells that can be delivered to the spinal cord to protect motor neurons. Their experiments are currently being conducted on animals. Hans Kierstead, Ph.D., of the University of California at Irvine, is developing stem cell-derived motor neurons for drug screening. His group has developed a way to package and preserve thousands of individual motor neurons in a testing plate that can be used by other groups to screen thousands of drugs quickly for their effects on the cells. This should accelerate the search for treatments.

False Claims and Clinical Trials

Larry Goldstein, Ph.D., of the University of California at San Diego spoke about the promise of stem cell research, but also cautioned the audience about false claims saying that it is important to remember that when it comes to unproven treatments, “the world outside the United States is the wild west.” Dr. Goldstein relayed the recently published story, sited on ISSCR website, of an Israeli boy with a neurodegenerative disease treated in Russia with stem cell infusions into the brain.  He is now suffering from multiple tumors because of the impurity of the cells. “Ensuring that people are protected from unscrupulous treatments is an appropriate role for the government,” he said, and urged anyone contemplating stem cell treatment outside the United States to visit the web site of the International Society for Stem Cell Research, at http://www.isscr.org/public/index.htm, to understand more about the risks and to learn important questions that should be answered before proceeding.

Dr. Koroshetz also stressed the importance of conducting rigorous clinical trials of new treatments. “I can’t tell you how many snake oils for ALS I’ve seen over my career.” Doing good trials “is not an easy process, as you all know. But it doesn’t mean we give up,” even when they are not successful, he continuted. “We go back to the drawing table and try something new. Eventually, we are going to get there, with the hard work of doctors and patients, especially the patients. I can't tell you when. We need luck and persistence, and the continued dedication of people like yourselves.”

One way to increase the number of clinical trials is to make them shorter, Dr. Bruijn pointed out, but this requires a “biomarker”—some way to tell right away if a treatment is altering the course of the disease. “If we had a biomarker, we could shorten trials to two or three months, instead of two or three years.” The Association has invested millions of dollars into the search for a reliable biomarker.

“All of these developments are very exciting,” Dr. Bruijn concluded. “We still have far to go, but I think there is more reason than ever to be optimistic about the development of treatments for ALS."

 

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