Researchers identify pathway that may slow the progression of Lou Gehrig's disease

April 12, 2000

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, 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 neurons.

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.

"Our study results are promising as they provide a foundation for evaluating drugs that could slow down the progression of ALS," says Dr. Friedlander, senior author of the study. "Although much more research needs to be conducted in this area, our research does bring us one step closer to finding a treatment for this tragic disease."

ALS is characterized by progressive loss of the motor neurons in the brain, brainstem, and spinal cord. On average, people who develop ALS die within five years of contracting the disease. Roughly 10 percent to 20 percent of ALS cases are hereditary.

All of the mice in the study were implanted with osmotic pumps that delivered zVAD-fmk, or a placebo, into the ventricles of the brain. They received the pumps at 60 days old, when the symptoms of the disease had not yet appeared, and received zVAD-fmk or placebo continuously for 56 days. The motor function of the mice was measured by timing how long they were able to stay on a rotating treadmill-like device called a Rotarod at a certain speed. The mice who received the highest doses of zVAD-fmk survived for an average of 153 days, as compared with 126 days for their untreated littermates, and were symptom-free for 20 days longer, on average.

The research was funded by the National Institute for Neurological Disorders and Stroke, the Muscular Dystrophy Association, the ALS Association, and Project ALS.
-end-


Columbia University Medical Center

Related Spinal Cord Articles from Brightsurf:

Stem cells can help repair spinal cord after injury
Spinal cord injury often leads to permanent functional impairment. In a new study published in the journal Science researchers at Karolinska Institutet in Sweden show that it is possible to stimulate stem cells in the mouse spinal cord to form large amounts of new oligodendrocytes, cells that are essential to the ability of neurons to transmit signals, and thus to help repair the spinal cord after injury.

Improving treatment of spinal cord injuries
A group led by UC Riverside bioengineering professor Victor G.

Spinal cord gives bio-bots walking rhythm
Miniature biological robots are making greater strides than ever, thanks to the spinal cord directing their steps.

Co-delivery of IL-10 and NT-3 to enhance spinal cord injury repair
Spinal cord injury (SCI) creates a complex microenvironment that is not conducive to repair; growth factors are in short supply, whereas factors that inhibit regeneration are plentiful.

Locomotor engine in the spinal cord revealed
Researchers at Karolinska Institutet in Sweden have revealed a new principle of organization which explains how locomotion is coordinated in vertebrates akin to an engine with three gears.

Neurological signals from the spinal cord surprise scientists
With a study of the network between nerve and muscle cells in turtles, researchers from the University of Copenhagen have gained new insight into the way in which movements are generated and maintained.

An 'EpiPen' for spinal cord injuries
An injection of nanoparticles can prevent the body's immune system from overreacting to trauma, potentially preventing some spinal cord injuries from resulting in paralysis.

From spinal cord injury to recovery
Spinal cord injury disconnects communication between the brain and the spinal cord, disrupting control over part of the body.

Transplanting adult spinal cord tissues: A new strategy of repair spinal cord injury
Spinal cord injury repair is one of the most challenging medical problems, and no effective therapeutic methods has been developed.

Gene medication to help treat spinal cord injuries
The two-gene medication has been proven to recover motor functions in rats.

Read More: Spinal Cord News and Spinal Cord Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.