SCIENTISTS SEARCH FOR DRUGS
TO TREAT KENNEDY’S DISEASE

HONOLULU, April 4, 2003 -- At the 55th Annual meeting of the American Academy of Neurology, scientists reported today that they’ve scored multiple “hits” in a screen for drugs that might be useful against Kennedy’s disease.

The disease, also known as spinal and bulbar muscular atrophy (SBMA), attacks muscle-controlling nerve cells in the spinal cord and the bulblike part of the brainstem, leading to muscle weakness and wasting (atrophy). Weakness often manifests by age 40, and is especially severe in the face and throat, interfering with basic functions like talking, swallowing and breathing.

The disease is caused by an expanded tract of DNA in the gene for the androgen receptor, a protein that enables cells to respond to testosterone and other masculinizing hormones.

Last year, the National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, Md., organized an ambitious project to identify drug treatments for SBMA and other neurological diseases. The agency established a collection of 1,040 compounds, most of which are drugs approved by the Food and Drug Administration, and selected about 30 research groups worldwide to test each compound against laboratory models of SBMA, amyotrophic lateral sclerosis (ALS), Huntington’s disease, Alzheimer’s disease and Parkinson’s disease.

Federica Piccioni, J. Paul Taylor and Kenneth Fischbeck of NINDS used cells harboring an “expanded” androgen receptor gene as a model of SBMA. They applied each of the 1,040 compounds to the cells, then measured the activity of caspase-3 – an enzyme that triggers nerve cell death in SBMA.

Some compounds actually increased caspase-3 activity, enhancing cell death, but 21 compounds inhibited the enzyme’s activity by 70 percent or more.

“A therapy that inhibits caspase-3 might be helpful in treating SBMA,” Piccioni said. She’s planning more laboratory tests on the 21 compounds to determine which ones appear safe enough and effective enough to move on to clinical trials.

As part of the NINDS project, MDA grantee Diane Merry of Thomas Jefferson University in Philadelphia also has conducted a screen for SBMA treatments. Results from the entire project are being prepared for publication, Fischbeck said.