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Animal study identifies potential treatment
for Huntington's disease
BOSTON - October 8, 2007 - MassGeneral
Institute for Neurodegererative Disease (MIND) researchers have
identified a compound that may lead to a treatment that could protect
against the effects of Huntington's Disease (HD). Their report,
which will appear in the Proceedings of the National Academy of
Sciences, describes how a small molecule called C2-8 appears to
delay the loss of motor control and reduce neurological damage in
a mouse model of the disorder. The study is receiving early online
release.
"We found that C2-8 slows the progress of HD in a mouse model
and might do the same thing in human patients, if it or its biochemical
relatives can be translated into a drug," says Steven Hersch,
MD, PhD, of MIND and the Massachusetts General Hospital (MGH) Department
of Neurology, who led the study. "What we don't know yet is
precisely how it works, what molecules it interacts with in cells
and how potent it might be."
C2-8 was first identified as a candidate treatment for HD by MIND
researcher Aleksey Kazantsev, PhD, based on its ability to block
the aggregation of the mutant huntingtin protein in yeast and animal
tissue and to improve function in a fruit fly model. The current
study was designed to further investigate its potential as a therapeutic
drug. The researchers first confirmed that oral doses of C2-8 can
cross the blood-brain barrier and are nontoxic in a mouse model
of HD. They also found that C2-8 does not interact with a number
of molecules predictive of negative side effects.
HD mice that were treated with C2-8 starting at the age of 24 days
scored significantly better on tests of strength, endurance and
coordination than did HD mice that did not receive the molecule.
While treatment significantly delayed progressive motor disability,
the animals receiving C2-8 did not live longer. Examination of brain
cells from the striatum, the area of the brain where the deterioration
of HD occurs, showed that treated mice had less shrinkage of brain
cells and smaller aggregates of huntingtin protein than did untreated
HD mice.
"We've both validated that compounds reducing the aggregation
of mutant huntingtin are potential HD drugs - so that strategy is
one that other scientists should pursue - and shown that C2-8 has
potential as the basis of a neuroprotective treatment," says
Hersch. "We now need to confirm those results in a different
mouse model, see whether similar compounds may be more potent than
C2-8 and search for the molecules it targets." Hersch is an
associate professor of Neurology at Harvard Medical School.
Vanita Chopra, PhD, and Jonathan Fox, PhD, of MIND and MGH-Neurology
are co-first author of the PNAS study. Additional co-authors are
Greg Lieberman, Kathryn Dorsey, Kazantsev and Anne B. Young, MD,
PhD, of MIND/MGH-Neurology; Wayne Matson, PhD, Boston University
School of Medicine; Peter Waldmeier, PhD, Novartis Institute for
Biomedical Research, Basel, Switzerland; and David Houseman, PhD,
Massachusetts Institute of Technology. The study was supported by
the Discovery of Novel Huntington's Disease Therapeutics Fund, MIND
and the Massachusetts General Hospital.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $500 million
and major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, systems biology, transplantation biology and photomedicine.
MGH and Brigham and Women's Hospital are founding members of Partners
HealthCare HealthCare System, a Boston-based integrated health care
delivery system.
Media Contacts: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
Information about Clinical Trials
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