Science Closer To a Treatment For Parkinson's By Michael Waldholz Staff Reporter of The WALL STREET JOURNAL ----------------------------------------------------- Researchers say experiments involving a powerful substance discovered in the hu- man nervous system, may lead to new drugs to slow the progress of Parkinson's disease and Lou Gehrig's disease. Four separate research teams are re- porting test-tube aid animal experiments showing the new substance acts as a biological shield, protecting crucial nerve cells from damage that normally kills them. Death of these cells is the hallmark of Parkinson's and amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease. The sulptance is perhaps most potent of series of human proteins - discovered In recent years by scientists at biotechnology companies - that the body uses to spur nerve-cell growth. The new growth factor was uncovered by researchers working separately at Synergen Corp., now owned by Amgen Inc., a biotech company in Thousand Oaks, Calif.; and by scientists at Genentech Inc., of South San Francisco, Calif. All four research teams conducted their experiments inassociation with one of the two biotechnology companies. It is unclear whether ownership rights for the substance will be disputed between Amgen and Genentech. But officials at both companies say that because of the promising results of the new experiments, they have decided to move forward to develop the substance as a potential treat- ment against Parkinson's and other nerve disorders. The new factor is called glial cell-line derived neurotrophic factor, or GDNF. Its discovery is so recent that scientists don't know exactly how GDNF spurs cell growth, or how it protects neurons from lethal dam- age. But the new experiments provide persuasive evidence that the factor plays an important role in the life cycle of neurons, and that scientists may be able to exploit that role in their search for new medicines against degenerative nerve dis- eases. GDNF "is by far the most powerful nerve growth factor wehave tasted yet," says Ronald Oppenheim. of Bowman Cray, School of Medicine, Winston-Salem. N.C., who led one of the research teams. Dr. Oppenheim's experiments in laboratory mice showed that GDNF kept alive almost all the cells that normally would have died within three weeks after researchers dam- aged them. "We were surprised because none of the other factors we've tested were that protective," he says. Still researchers emphasize that the new results are preliminary, suggest- lng that many years of work will be needed before they know GDNF or some related chemical will be helpful to patients. Indeed a similar kind of nerve-growth factor called CNTF, developed by the bio- tech company Regeneron Pharmaceuti- cals Inc., Tarrytown, N.Y., produced trou- bling side effects when tested last year in ALS patients. Regeneron, Amgen, Genen- tech and several other biotech companies are researching other, promising nerve- growth factors. Even so, the new experiments, pub- ---------------------------------------------- Four Research Teams Move Closer to Drug For Parkinson's, ALS *Contunued from Page B1* ---------------------------------------------- lished today in the British Nature, provide several hints that in uncovering GDNF, scientists have, found a now door-, way to the treatment of nerve diseases that continue to defy adequate treatment. "It's a fairly exciting set of results," says Ronald Lindsay, vice president for neuro- biology research at Regeneron, noting that "it prvides strong competition for the [factors] we've been working with." In several experiments using GDNF developed by Synergen and now owned by Amgen, researchers used the substance to protect nerve cells from destruction caused by a toxic substance called MPTP. When given to mice. MPTP produces symptoms similar to the debilitating muscle tremors caused by Parkinson's disease in hu- mans. In one surprising experiment by scien- tists at Karolinska Institute in Stockhom and at Snergen in Boulder, Colo., GDNF restored nerve activity to cells already damaged by the MPTP toxin. GDNF was first isolated in 1990 by Frank Collins, a biologist working at Syn- ergen. He identified it in glial cells, which provide nutrients to neurons. Dr. Collins didn't publish the discovery until 1993, when Synergen received a patent. About the same time, Dr. Collins was hired by Amgen. In an interview, Dr. Collins said that acquiring the rights to GDNP was one of the reasons Amgen bought Synergen several months ago. "I've been given the green light to go full steam ahead In developing GDNF for use against Parkinson's disease," says Dr. Collins, senior director of neuroscience research at Amgen. He said. it may be possible to begin testing the substance In humans within a year or two. Currently. the symptoms of Parkin- son's disease can be treated with several medicines, but their effectiveness wftm off after time. Amgen hopes GDNF can protect nerve calls being relentlessly killed, by the disease, thereby prolonging the existing treatments' usefulness. Buy GDNF will do nothing to stop the underly- ing cause of the illness, which is still unknown. A significant hurdle facing GDNF is that cells under attack by Parkinson's are located in the brain. Because GDNF is a large molecule that can't get into the brain if ingested or injected into the blood- stream, it will have to be infused directly.