Discovery Suggests Strategies for Drug Treatment of Disease in Humans
Columbia researchers have participated in a new study that points toward a potential treatment for amyotrophic lateral sclerosis (ALS), also
known as Lou Gehrig’s disease.
The study was led by Dr. Robert M. Friedlander of Harvard Medical School and the Brigham and Women’s Hospital Neuroapoptosis Laboratory and Neurosurgical Service, will be published in the April 14 issue of Science. Dr. Serge Przedborski, an associate professor of neurology and pathology in Columbia’s College of Physicians & Surgeons, was the main collaborator in the study that also involved researchers from the University of Chicago’s Department of Medicine.
The study employed mice genetically engineered to have a mutation in the superoxide dismutase-1 gene (SOD-1), the same mutation found in the familial or hereditary form of ALS. Caspases are enzymes that are unleashed in apoptosis, or planned cell death, to destroy cells that are no longer needed or are abnormal.
Researchers believe that in neurodegenerative diseases like ALS, the process of caspase-mediated apoptosis is misdirected and begins to destroy
In the study, mice given a compound called zVAD-fmk that blocks the action of caspases developed ALS-like symptoms later and lived 22 percent longer than the mice who did not receive the drug.
Dr. Przedborski points out that while zVAD-fmk inhibits several caspases at once, pharmaceutical companies have compounds under development that may inhibit caspases more specifically. He calls the study “proof of principle” that a caspase-inhibiting drug could help delay onset of symptoms and prolong life in ALS patients.
Currently, no treatment exists for ALS. “Virtually all our patients are dying,” Dr. Przedborski says. “We can prolong life with mechanical ventilation, we can temporarily improve their quality of life with different strategies, but ultimately our patients are dying.”
Dr. Przedborski notes that caspase inhibitors would not be a miracle drug and would not cure ALS. However, he suggests that a “cocktail” of drugs that attack the neurodegenerative process at several different points–similar to the successful strategy now used to treat HIV infection–could one day be used to slow the development of symptoms and prolong survival in ALS patients.