TIME EUROPE
January 15, 2000, Vol. 157 No. 2
The Hunt for Cures
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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."
Just as important as protecting healthy neurons is repairing or replacing nerve cells that have been damaged. The body produces a whole bath of trophic — or growth — factors that help cells develop. If the brains of Parkinson's patients could be fortified with additional trophic doses, many scientists believe, damaged neurons might be reawakened or repaired. While there is some thought in the medical community about engineering genes to churn out the substances, the pharmaceutical industry is taking a more direct approach.
Currently, Guilford Pharmaceuticals in Baltimore, Md., and Amgen in Thousand Oaks, Calif., are collaborating on a synthetic neurotrophic compound that can be taken orally and then travels to the brain, where it bonds with proteins in dopamine neurons. The tricky part is that most trophic molecules are too big to move across the miniscule blood vessels in the brain, so Guilford and Amgen are working on a smaller one that can get where it needs to go. The progress so far is promising. "We're in Phase 2 human trials now," says Dr. Craig Smith, president of Guilford. "Although we don't have results yet, if the drug proves safe and extremely effective in trials, it could be on the market as early as 2005."
Whether such an anti-Parkinson's potion is really so close at hand is unclear, but scientists are not waiting to find out. Other possible treatments under study include boosting antioxidants, which would protect brain cells from free radicals, highly reactive molecules that are by-products of oxidation; and blocking the body's production of compounds called excitatory amino acids, which can cause neuron damage. It's hard to say which, if any, of these treatments will succeed, but with science closing in from so many directions, it's possible that for the first time, Parkinson's disease may find itself on the run.
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COVER STORY
Special Report: The Future of Medicine
With the mapping of the human genome the process by which new drugs are developed is being turned upside down. These drugs will also change our lives
Brave New Pharmacy
Using high-speed robots and the secrets of the human genome, scientists are changing forever the way they discover new medicine
The Hunt for Cures
Genetic information could lead to treatments for everything from AIDS to obesity
EUROPE
Prague Winter
When Jiri Hodac was named director of state television, Czech journalists saw a return to government meddling in the media
See Vous in Court
France is the latest nation to join the litigation game
Going up in Smoke
Switzerland, land of luxury watches and bank secrecy, has a new growth industry: marijuana
UNITED STATES
The True Blue Bush Cabinet
Its ethnic and gender balance is correct, but can a divided nation deal with the superconservative bent?
BUSINESS
Transparency has its Price
Executives at many German companies are finding it hard to adjust to the more rigorous financial disclosure required by global investors
On Spreading the Word
When it comes to selling merchandise, word-of-mouth marketing may be a company's best weapon
Essay: Meat Matters
Critics of industrialized farming may be forgetting about world hunger, writes TIME's Rod Usher
THE ARTS
Rebel with a Cause
The real-lifestory of an anti-Mafia activist in Sicily makes for a handsome film with a political message
The Upmarketeer's Tale
Bernard Arnault built his house by selling at deluxe prices and in his book he's still giving nothing away
The Art of Noise
For Europe's freely improvised music, the only rule is no rule
DEPARTMENTS
Techwatch
World Watch
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