SAN ANTONIO — A drug already used in some leukemia patients prevented brain cells linked to Parkinson's disease
from being destroyed in mice, a finding that could point to a way to
slow progression of the disease, San Antonio researchers are reporting.
The research is early, and the drug used in the experiment doesn't work well in the human brain.
But similar drugs are in development that might better penetrate the
brain as well as target the specific enzyme at fault more precisely,
scientists said.
The researchers first discovered a mechanism at work in Parkinson's disease that prevents a protein called parkin from doing its job of keeping the brain clear of other proteins that can accumulate and kill off cells.
An enzyme linked to chronic myeloid leukemia
blocks parkin from working, they found. When a leukemia drug was used
in turn to block the enzyme - called tyrosine kinase c-Abl - it
prevented destruction of those healthy cells.
The results were being published Wednesday in the Journal of Neuroscience.
Half-million sufferers
About a half-million
people suffer from the tell-tale tremors and stiffness of Parkinson's,
which is caused by damage to the dopamine-producing cells in the brain.
"In Parkinson's
disease, we know the number of patients is increasing," said Syed Imam,
the lead author of the paper and an adjunct assistant professor of medicine at the University of Texas Health Science Center.
"The (current) treatments are mostly to improve symptoms. They do not
address how to slow down the disease. Our studies were targeted at
whether we could actually slow the progression."
Imam, who joined the staff of the U.S. Food and Drug Administration
after the research was completed, cautioned that the findings must
still be duplicated in larger animals and then in people. But he said he
was encouraged the same mechanism was confirmed in brain tissue taken
from people who died of Parkinson's.
A mutation in the
gene that produces parkin is known to cause an inherited form of
Parkinson's disease that makes up less than 5 percent of total cases.
Parkin was suspected in other cases, but the exact cause was unclear.
Fox Foundation involved
"They're showing
that this molecule, c-Abl, when it is activated, it actually inactivates
parkin and blocks its protective effects," said Dr. Beth-Anne Sieber, a
program director at the National Institute of Neurological Disorders and Stroke, which partly funded the research along with the Michael J. Fox Foundation,
the San Antonio Area Foundation and others. "If you inhibit c-Abl
activation, it lets parkin pursue its normal protective cell function."
The drug - sold as
Gleevec - doesn't penetrate the brain very well, and doesn't just block
c-Abl. But it's been on the market for several years and is well
studied, the researchers noted, while newer, more specific drugs are in
the pipeline.
"We're excited about
this because it does provide a specific mechanism in Parkinson's," said
Dr. Robert Clark, assistant vice president for clinical research at the
health science center, and a co-author of the paper. "It's likely not
the only mechanism. It's one of several different things going on in the
course of Parkinson's. But it's exciting, too, because it's a pathway
that can be targeted therapeutically."
dfinley@express-news.net