July 11, 2006
Research Update — from ALSA’s National Office
New Article About Promising Compounds
Roberta Friedman, Ph.D., ALSA Research Department Information Coordinator
An article that discusses compounds that show promise for treating amyotrophic lateral sclerosis (ALS, also called Lou Gehrig’s disease) has been published in Neurology. The consensus that these potential treatments for the disease are appropriate to enter clinical testing in ALS came from collaborative discussion among ALS experts and the ALS community. The process will inform future selection of new therapies for accelerated clinical testing in ALS to speed discovery of effective treatment for this inevitably fatal disease.
Two of the drugs in the currently published list have already shown promise in early (Phase II) clinical trials in ALS. These compounds are talampanel and tamoxifen. Larger trials that are designed specifically to show efficacy (Phase III) are required to see if these drugs could help in the disease. Others of the drugs listed are already in Phase III trials. These include ceftriaxone, minocycline, ONO-2506 and IGF-1 polypeptide.
The remaining drugs require more pre-clinical data and toxicology testing in people before they can be entered into a large patient trial in ALS.
A total of 20 existing compounds are listed in the report as showing the most promise for treating the disease. These were selected after review and discussion of the original 113 compounds that the scientists had identified from existing information. The consensus approach used will surely help as new clinical candidates emerge, especially with the new initiative by The ALS Association, called TREAT ALS (Translational Research Advancing Therapy for ALS), a drug discovery program and clinical trials process that accelerates discovery and testing of new compounds through rapid screening and testing in cell and animal models of the disease.
The experts who authored the report are Lucie Bruijn, Ph.D., vice president and science director of The ALS Association, as well as Brian Traynor, M.D., a fellow at the National Institutes of Mental Health, Robin Conwit, M.D., of the National Institute of Neurological Disorders and Stroke, Flint Beal, M.D., of Cornell University Medical Center, N.Y., Gilmore O'Neill, MB, MRCPI, MMedSc, Biogen Idec, Susan Fagan, PharmD, of the University of Georgia in Augusta, and Merit Cudkowicz, M.D., a clinical investigator at the Massachusetts General Hospital.
Multiple biochemical pathways are implicated in the disease process of ALS, and accordingly, the list of proposed compounds for priority testing includes drugs that act on different aspects of the biology of the motor neuron, the cell that dies in the disease. Combinations of these proposed drugs may well prove to be the most helpful way to treat the disease.
The researchers who evaluated the drugs tried to be clear about any bias they might have toward drugs under investigation in their own labs. All data relevant to the review of the compounds were made available to the ALS community during the discussions.
The ALS Association has encouraged clinical investigators to submit proposals for pilot studies that would investigate single or combination therapy with drugs on the list. TREAT ALS is also a drug discovery program, so new molecules that will emerge can be considered in the framework established and described in this publication and prioritized. In this way, TREAT ALS will readily translate findings from basic research into streamlined patient trials.
For further information, click on http://www.alsa.org/research/article.cfm?id=678 and http://www.alsa.org/patient/drug.cfm.
