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Aiming At Multiple Alzheimer's Proteins May Be Key To Success
An independent team of
scientists is leading Alzheimer's disease research in a new, promising
direction. Through a $1 million grant they received last year from
Alzheimer's Disease Research, a program of the American Health Assistance
Foundation (AHAF), Donald F. Weaver, M.D., Ph.D. and his colleagues at
Dalhousie University in Halifax, Nova Scotia, Canada are leading a
multi-site, multidisciplinary international effort to design a drug that
might one day prevent the onset of this devastating disease.
In Alzheimer's disease, an accumulation of beta amyloid protein
"plaques" around the brain's nerve cells and tau protein "tangles" within
these cells is connected to a breakdown in cell communication and eventual
cell death. Evidence suggests that both beta amyloid and tau play a role,
but the research community has been split on the relative effect of these
two proteins on the disease process. Further, many scientists are beginning
to believe that future Alzheimer's therapies will involve multiple drugs
targeted at different aspects of the disease, including both of these
proteins. They theorize that "misfolding" of each protein changes its shape
and natural function, and contributes profoundly to the development of
Alzheimer's disease. Dr. Weaver and his colleagues from Canada, the U.S.,
and Belgium agree that the key to successful treatment may be to halt the
build-up of both beta amyloid and tau, before they begin to affect the
brain's nerve cells. "Alzheimer's disease is a complex ailment and may have
overlapping causes," explains Dr. Weaver. "Disrupting beta amyloid
misfolding may work for some people, but not others. The same is probably
true for tau. If we could control both proteins in the same patient, we
might get a synergistic benefit." Rather than seeking multiple drugs to
accomplish this task, Dr. Weaver's team is looking for single molecules
that will bind to both proteins and possibly other Alzheimer's-related
proteins before they begin to misfold and start their toxic buildup. "Right
now, we're treating the symptoms of the disease -- only slowing cognitive
decline and memory loss in patients," says Dr. Weaver. "My colleagues and I
are using this grant to design drugs that may one day prevent or even
reverse progression of Alzheimer's disease."
The design strategy begins at Dalhousie University where researchers
are creating new, unique drug compounds and testing each drug's ability to
bind to both proteins and prevent shape changes. To date, Dr. Weaver's
laboratory has produced more than 240 variations of the most effective
compound. Once identified, these synthesized compounds are sent for further
analysis to Edwin De Pauw, Ph.D. and his group at the University of Liege
in Belgium. Promising compounds that pass this second step in testing then
move on to preliminary safety and efficacy investigations using animal
models in the laboratory of Ottavio Arancio, M.D., Ph.D. at Columbia
University Medical Center in New York.
Since accepting the award from AHAF last year, this international team
has made impressive progress. These easily reproducible chemical compounds
have shown a remarkable ability to prevent misfolding of both proteins in
the Dalhousie laboratory. This activity has been confirmed at the
University of Liege, and exciting results are reported at Columbia. "Our
lead compound is very effective in mice with conditions similar to
Alzheimer's. It can be delivered orally, inhibits aggregation of these
proteins, protects brain cells from beta amyloid damage, restores normal
memory functioning and shows no toxicity at high doses," says Dr. Weaver.
According to AHAF's Director of Research Grants, Guy Eakin, Ph.D., "This
work is particularly important because Alzheimer's disease patients are
often taking several medications for other health conditions. Rather than
give them a 'cocktail' of drugs that might produce harmful interactions,
Dr. Weaver's research shows it may be possible to limit these concerns by
designing a single drug that tackles several factors."
This project has been substantially funded by one of two $1 million
"Centennial Awards" from Alzheimer's Disease Research, a program of AHAF.
To foster stronger collaboration among researchers, these unique awards
were given only to scientists working with interdisciplinary colleagues at
multiple institutions.
About AHAF
AHAF is a private, donor-supported non-profit organization dedicated to
finding cures for Alzheimer's disease, macular degeneration and glaucoma by
funding the best research worldwide, and to informing the public about
these age-related, degenerative diseases.
Available Topic Expert(s): For information on the listed expert(s),
click appropriate link.
American Health Assistance Foundation
http://www.ahaf.org
Cu scopul de multiple Alzheimer Proteins Poate fi cheia succesului - Aiming At Multiple Alzheimer's Proteins May Be Key To Success - articole medicale engleza - startsanatate