POSITIVE RESULTS IN MICE SET STAGE FOR CELEBREX TRIAL IN ALS

SAN DIEGO, Nov. 12, 2001 -- Encouraged by results from a study on mice, an MDA-funded research group is ready to launch a clinical trial of Celebrex in amyotrophic lateral sclerosis (ALS). Jeffrey Rothstein of Johns Hopkins University in Baltimore reported the impressive results of the mouse trial during the 31st Annual Society for Neuroscience meeting in San Diego Sunday.

Celebrex, manufactured by Pharmacia (under the generic name celecoxib), is a hot new arthritis drug that works by selectively inhibiting COX-2 — an enzyme in the body responsible for manufacturing pro-inflammatory hormones called prostaglandins.

In recent months, following evidence that overactivity of COX-2 might contribute to ALS, neurologists Rothstein and Daniel Drachman at Johns Hopkins began planning a trial of Celebrex in people with ALS. (Drachman and Rothstein are co-directors of the MDA/ALS Center at Hopkins.)

Their groundbreaking research began with experiments on motor neurons -- the muscle-controlling nerve cells in the spinal cord that are killed by ALS. The loss of those motor neurons leads to paralysis and death in people with ALS, usually within three to five years of diagnosis.

Drachman and Rothstein found that Celebrex could protect motor neurons from toxic levels of the brain chemical glutamate. Around the same time, MDA grantee Serge Przedborski of Columbia University in New York showed that the activity of COX-2 is unusually high in spinal cords of ALS patients.

In a recently completed study in a mouse model of ALS, Rothstein said, Celebrex delayed disease onset by 54 days and prolonged survival by four weeks in the mice, which carry a mutant version of the SOD1 gene that's been linked to familial ALS.

Rothstein said the effect shows that Celebrex is more powerful than riluzole (Rilutek), the only FDA-approved drug for ALS. In the mice, riluzole prolongs survival by two weeks, and in people with ALS, it extends life by only a few months.

With the mouse study results in hand, Rothstein says the clinical trial of Celebrex has been approved by a Johns Hopkins review committee, and is now open for enrollment.

The trial will take place at 25 centers across the country, and is seeking to enroll 300 participants.