The Hunt For Cures: Parkinson's Disease: Lubricating Gummed-Up Brains

It's hard to imagine asking a doctor to destroy a part of your brain. For the more than 1 million Americans suffering from Parkinson's disease, however, such a drastic measure--in which an electrode is used to kill tremor-causing neurons--may become necessary.

The irreversible procedure is just one of many therapies, both surgical and pharmacological, that Parkinson's patients have tried over the years to control the tremors, rigidity and other symptoms that characterize the disease. All the treatments offer some relief, but none can remotely be called a cure. Now that may be changing. The further scientists peer into the human genome, the more they are uncovering the secrets of Parkinson's--and the more they are becoming convinced that next-generation drugs may at last be able to beat back the disease. What's more, the benefits may not be limited to Parkinson's but may also be used to treat Huntington's, Lou Gehrig's and even Alzheimer's disease--all of which have similar neurodegenerative roots and may respond to similar drugs. Says neurobiologist Michael Zigmond of the University of Pittsburgh: "A breakthrough in any of these diseases could have an impact on the others."

The first place to look for causes of and treatments for Parkinson's disease is in the brains of patients. As the illness worsens, brain tissue becomes clogged with a protein muck that includes a substance called alpha-synuclein. No one knows exactly what alpha-synuclein does, but it's believed to play a role in the smooth transmission of nerve signals. When the substance clumps, it can't do the work it was designed to do, leading to neuron damage, loss of the neurotransmitter dopamine and eventually the familiar shakiness of such well-known Parkinson's sufferers as Janet Reno and Muhammad Ali.

The hunt for a Parkinson's cure got a boost in 1997 when researchers discovered a handful of patients whose alpha-synuclein genes had mutated. This might seem like open-and-shut evidence that the cause of the illness had been found, except that the vast majority of Parkinson's patients, whose brains also grow gummed up, do not carry the mutation. Still, scientists believe that the bad gene is a powerful clue. "There appear to be more clumps in the brains of people with the mutant gene," says Zigmond. "Learning how the protein functions may help us develop drugs that target it."

Another gene, newly dubbed the parkin gene, has also been getting a lot of attention. In 1998 Japanese researchers reported on studies conducted on five young patients with early-onset Parkinson's, all of whom carried a recessive gene that appeared to be associated with the disease. Though relatively rare, the parkin gene is much more common than the defective alpha-synuclein gene, and in places like China, with high rates of early-onset Parkinson's, it may play a role in a significant number of cases. Just last October, researchers at Duke University Medical Center went a step further, reporting their discovery of a previously unseen mutation on the parkin gene that appears to link it to late-onset forms of the disease as well. "Once we figure out how that gene functions," says neurology professor Ira Shoulson of the University of Rochester Medical Center, "we could perhaps disrupt it pharmacologically."