A natural compound found to be extraordinarily potent in protecting nerves from harm in a lab model of amyotrophic lateral sclerosis (ALS) will likely usher in a new drug "cocktail" approach to the disease, according to Johns Hopkins scientists.

ALS, also known as Lou Gehrig's disease, brings about a slow death of motor neurons -- the nerve cells that activate muscles -- in the spinal cord. Patients become progressively weaker until muscle use is entirely lost.

In the Hopkins studies, however, pigment epithelium-derived factor, or PEDF, safeguards nerves in the animal spinal cords that serve as models, "offering nearly complete protection," according to neurologist Ralph W. Kuncl, M.D., Ph.D., who led the research team. The research report appears in this month's Journal of Neuropathology and Experimental Neurology.

"If we had this same level of protection in patients with ALS, they'd experience slight muscle weakness at most," says Kuncl. "It's early," he adds, "but because PEDF appears so potent and seems to lack toxicity, these results are unusually promising." The team next plans to test PEDF in transgenic mouse models of the disease.

In the study, researchers pinpointed PEDF for the first time in the spinal cord and skeletal muscle of humans, monkeys and rats. Prior to this, scientists thought the eyes were its prime location, in the pigmented layer of cells underlying the retina. Then, using slices of rat spinal cords kept alive in culture, the Hopkins researchers tested PEDF's ability to protect cells against the toxin THA (threo- -hydroxyaspartate), a drug that brings about slow death of motor neurons and thus mimics essential features of ALS.

PEDF-treated sections averaged near-normal neuron counts compared with untreated ones. Levels of a key enzyme typically made by healthy cells underscored the result. "PEDF may significantly protect spinal motor nerves ag
'"/>

Contact: Marjorie Centofanti
mcentofanti@jhmi.edu
410-955-8725
Johns Hopkins Medical Institutions
6-Jul-1999