Caffeine


By Neil Osterweil
WebMD Medical News
Reviewed by Dr. Charlotte E. Grayson

Oct. 17, 2000 (Boston) -- Parkinson's disease (PD) is an illness that
progresses slowly, and so, it seems, have medical science's efforts at
finding ways to fight it. Nonetheless, researchers at a national meeting of
neurologists here say they are making steady, incremental gains in their
battle against the disease.
One of the notable researchers attending the meeting -- Nobel laureate James
D. Watson, PhD, who was a co-discoverer of the structure of DNA in the
1950s -- predicts that the answer may lie in the field of genetics.
"Parkinson's is not an infectious disease, so it must therefore have a
genetic basis," he tells WebMD.
Indeed, the latest news in the battle against Parkinson's involves
genetics -- or at least gene therapy. German researchers speaking at the
meeting Tuesday report that they have devised a gene therapy "cocktail" that
appears to protect critical brain cells in mice with disabling conditions
similar to PD in humans.
Theirs is one of several new studies describing promising, but still
experimental, treatment approaches for Parkinson's. Up to 1.5 million
Americans suffer from PD, which causes such symptoms as uncontrolled
trembling, muscle rigidity, and a loss of the ability to control movement,
according to the National Parkinson Foundation. Over time, people with
Parkinson's may develop trouble walking, talking, or completing other simple
tasks that involve movement.
Just this week, a study was published in the Journal of the American Medical
Association in which Harvard School of Public Health researchers show that
moderate consumption of caffeine may reduce the risk of developing PD for
men, and possibly for women, too. In the study of more than 130,000 people,
the men who consumed the most caffeine -- primarily in the form of coffee --
 were least likely to get PD during their lifetimes. Women who drank one to
three cups of coffee a day also appeared to be protected from Parkinson's,
but the study seemed to show that drinking more than three cups a day was
too much of a good thing for women.
This week also saw the release of a study showing that a new type of drug
for Parkinson's appears to offer benefits over the standard therapy,
levadopa. Levodopa, marketed as Sinemet or Atmet, is effective in delaying
the progression of PD, but often causes severe side effects, including
involuntary movements and restlessness. In the study, patients with early
signs of PD who took the new drug -- Mirapex -- had a 55% reduced risk of
developing movement problems, compared with patients taking levodopa. The
findings echoed those of a Canadian and European study of a similar drug --
Requip -- that was published earlier this year.
The gene therapy study focused on cells that produce a chemical called
dopamine. Parkinson's is caused by the progressive death of nerve cells in
the brain that produce dopamine, which helps the central nervous system to
control bodily movements. The researchers attempted to deliver to the mice's
brains substances that could protect the dopamine-producing nerve cells from
dying off, and ideally, help them keep pumping out dopamine as usual.
The gene therapy cocktail they created is composed of common, harmless cold
viruses that are altered to carry genes for two such substances: one that
may keep the cells from dying prematurely (through a process known as
programmed cell death), and the other a growth factor that some studies have
shown can keep the brain's dopamine-making and dopamine-receiving nerve
cells in the peak of health.
"What we have done here is, first, a proof of principle that a gene
therapeutic approach is working, [and] second of all, that the combination
of a ... protective therapy, together with a [nerve cell-restoring] therapy,
works," study author Jörg Schulz, MD, an assistant professor of neurology at
the University of Tubingen in Germany, tells WebMD.
When they injected the altered viruses into the brains of mice with the
Parkinson's-like disorder, they found that neither the substance that blocks
cell death nor the growth factor alone was particularly effective at
protecting the brain cells. But the two in combination did appear to
preserve the cells and their function.
This novel therapy is now limited by the relatively short time that the
genes stay active after injection -- the viruses eventually are recognized,
and destroyed, by the body's immune system. In addition, the viruses cause
inflammation and swelling, which also can cause the protective genes to shut
down prematurely.
"The concept of combining treatment approaches is, I think, an attractive
one," says A. Jon Stoessel, MD, a professor of neurology at the University
of British Columbia in Vancouver, who reviewed the research for WebMD. "Now
the practicality of it in the long term, the relevance of the mouse ...
model to humans, and the ability to salvage [nerve cells], as well as reduce
toxicity, are all issues that I think are going to have to be addressed."
There's also an additional concern: Because programmed cell death is a
mechanism by which the body rids itself of harmful or dying cells,
interfering with it could promote the growth of cancers, which are primarily
caused by the unchecked growth of abnormal cells.
Schulz tells WebMD that the researchers will be following the mice as they
age to monitor them for any side effects from the gene therapy. At any rate,
it will be several years before the experimental therapy can make the leap
from mice to men and women, he emphasizes.
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