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Science Highlights-1998 By Joe Bruman January 1999 (This continues the series of annual reviews, with slightly different titles, for 1995, 1996, and 1997.) DRUGS: The COMT inhibitor entacapone (Comtan) hasn't quite reached final approval, but trial reports are good and it should be soon. Tolcapone (Tasmar) made a glorious start, but came a cropper because of its suspected liver toxicity. One death among the many trial subjects, cited in the original package insert, drew little attention from enthusiastic users. But two more cases, even though evidence for a causal link is only circum- stantial, have prompted official restrictions. Cabergoline (Dostinex) got excellent reviews but was withheld from the U.S. market for business reasons. Whether selegiline (Eldepryl) shortens lifespan was still being debated and analyzed by statisticians, who lean toward "not proven". Likewise for neurotoxicity of levodopa: Some therapists favor avoiding it in young, new patients, while others feel that it is harmless and that its benefits can't be matched by dopamine agonists alone. ETIOLOGY: Contrary to former belief, some human brain neurons can indeed regenerate, and even though they aren't of the areas affected by PD, there is new hope. Smokers still are less likely to have PD, but only if they are among the approximately half of all whites who share a particular form of the gene for MAO-B. Workers are still searching other populations for the mutant alpha-synuclein gene of the Contursi familial PD cohort, but no luck. At last, a clue to the environment/heredity puzzle: People exposed to pesticides are more likely than others to develop PD, but only if they also carry a mutant gene for glutathione S- transferase, an enzyme that normally destroys such neurotoxins. DIAGNOSTIC TOOLS: The new technique of magnetic resonance spectroscopy, still limited to research applications, goes a step beyond MRI. It can show the distribution not only of tissue, but also of specific compounds such as dopamine, and where they are concentrated. New clinical tests should make it easier to distinguish PD from other neurodegenerative diseases such as PSP or MSA, earlier in their course. Enhanced fatigue, or exercise intolerance, in PD is getting belated attention. Unlike ordinary fatigue, it's not associated with mitochondrial function, and it does respond to levodopa. SURGERY: Deep-brain stimulation is getting popular, and is being used to explore the brain for new sites of intervention. It appears that DBS will be able to provide all the symptomatic benefits of pallidotomy or thalamotomy, with the added virtue that it may be adjusted or stopped at will. Any invasion of the brain, whether for DBS or conventional ablation surgery, carries the risk of injury. Recipients with previous cardiovascular disease are more likely to suffer a stroke, sometimes several weeks after such surgery. Trials of pig fetal cell transplants for PD appear generally successful, but officials are getting more concerned over the risk of trans-species infection, even though no actual instance has been reported as yet. Cheers, Joe -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013