Research Roundup updates as of December 2004:
Gulf War report available online
The Research Advisory Committee on Gulf War Veterans’ Illnesses has published online its full report, originally released in September.
You can read it at www.research.va.gov/resources/pubs/docs/GulfWarRpt04.pdf as a pdf file, requiring Adobe Acrobat software.
The report includes 152 pages of analysis and recommendations concerning symptoms experienced by U.S. military personnel deployed during Operation Desert Storm in 1990 and 1991.
Some of the findings follow.
- Many who served in the Gulf War were exposed to a variety of potentially toxic substances during their deployment. Among these were several neurotoxins — chemical nerve agents, medications taken to protect troops from anticipated effects of poison nerve agents, and several types of pesticides. All these belong to a class of compounds known to adversely affect the nervous system.
- All or most of the chemical agents to which the soldiers were exposed counteract the enzyme acetylcholinesterase, which normally breaks down the chemical acetylcholine. Acetylcholine carries signals in the nervous system and from nerve to muscle cells. Prolonged and excessive acetylcholine signaling is proposed as a possible source of nervous system damage in Gulf War participants.
- Gulf War veterans differ from a healthy control (comparison) group on measures of neurological pathology and impairment. Gulf War veterans have developed ALS at twice the rate of their nondeployed counterparts.
- Contrary to previous assumptions, exposure to nerve agents at levels too low to produce acute symptoms can result in chronic adverse effects on the nervous and immune systems.
- Congress should allocate at least $45 million for research on Gulf War illnesses, to be divided among the Departments of Veterans Affairs, Defense, and Health and Human Services.
"We need to study more specifically these agents that were used," says Hiroshi Mitsumoto, co-director of the Eleanor and Lou Gehrig MDA/ALS Center at Columbia University in New York. "There are a number of questions we need to answer."
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Report shows tamoxifen safe, maybe beneficial
An interim analysis of an ongoing trial of the breast cancer drug tamoxifen (Nolvadex) in 60 people with ALS demonstrates that the drug appears to be safe and may even improve survival in the disease.
Benjamin Brooks, a neurologist who directs the MDA/ALS Center at the University of Wisconsin at Madison, received funding from MDA and the National Institutes of Health to test tamoxifen, after a patient of his who had both ALS and breast cancer, for which she received tamoxifen, maintained muscle strength for more than four years.
Participants in three groups who took high-dose tamoxifen combined with the ALS drug riluzole (Rilutek) showed a four- to six-month survival advantage compared to the two groups who took a low dose of tamoxifen plus riluzole. The low-dose groups showed survival similar to that seen in people treated with a placebo (inert substance) in other ALS studies.
There were no significant side effects.
Brooks reported these preliminary findings in Philadelphia last month at the 15th International Symposium on ALS/MND, organized by the Motor Neurone Disease Association. The study hasn’t yet been completed.
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High-dose CoQ10 looks safe in long-term study
MDA research grantee Merit Cudkowicz, at Massachusetts General Hospital in Boston, announced at last month’s ALS symposium in Philadelphia that her study of 31 people with ALS who took a high dose — up to 3,000 milligrams — of coenzyme Q10 for eight months tolerated the drug well. The only side effects were gastrointestinal and were considered mild.
The dietary supplement is thought to improve the function of the mitochondria, the energy-producing units inside cells.
In August, researchers at Columbia University Medical Center in New York reported similar results in their study of the safety and tolerability of coQ10 in ALS, but that study was shorter and used lower doses.
The National Institute of Neurological Disorders and Stroke of the National Institutes of Health has approved funding for a multicenter study of coQ10 in ALS that will include MDA/ALS centers at Columbia and Massachusetts General.
For information about this study, which is just getting under way, contact Alexandra Barsdorf (212) 342-3026 or email@example.com.
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VEGF protein infusion helps rats with ALS
Vascular endothelial growth factor (VEGF), a protein that appears to promote blood vessel growth and protect nerve cells, continues to show promise in laboratory experiments in rodents.
A Belgian and Dutch scientific team found that delivering the VEGF protein (for which the VEGF gene provides instructions) into the brains of rats with ALS showed significant benefit. The team was led by MDA research grantee Peter Carmeliet, of the University of Leuven and the Flanders Interuniversity Institute for Biotechnology, both in Belgium.
Such a strategy might provide a shorter route from laboratory to clinic than would a gene-based therapy, which has to go through more regulatory steps.
The investigators, who published their findings online Nov. 28 in Nature Neuroscience, found that injecting the VEGF protein into a fluid-filled space (ventricle) in the rats’ brains delayed paralysis and prolonged survival.
In rats genetically destined to develop ALS, paralysis appeared 17 days (16 percent) later in rats who received VEGF at two months of age than in those treated with fluid alone.
Both groups of rats developed the disease, but the treated rats lived 22 days (18 percent) longer.
Rats that received VEGF treatment at nearly three months, after symptoms had already appeared, lived 10 days (8 percent) longer than their untreated counterparts.
"In summary," the authors write, "our data indicate that VEGF may assist in slowing down [nerve cell] degeneration and warrant further studies to clarify the relevance of VEGF delivery for the ALS community."
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