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Novel Antibodies for Combating Alzheimer’s and Parkinson’s Disease
Researchers at Rensselaer Polytechnic Institute
Develop Antibodies With Improved Ability for Preventing
Formation of Toxic Protein Particles Linked to Diseases
Including Alzheimer’s and Parkinson’s
Antibodies developed by researchers at Rensselaer Polytechnic Institute
are unusually effective at preventing the formation of toxic
protein particles linked to Alzheimer’s disease and Parkinson’s
disease, as well as Type 2 diabetes, according to a new
study.
The onset of these devastating diseases is associated with
the inappropriate clumping of proteins into particles that are
harmful to cells in the brain (Alzheimer’s disease and
Parkinson’s disease) and pancreas (Type 2 diabetes).
Antibodies, which are commonly used by the immune system to
target foreign invaders such as bacteria and viruses, are
promising weapons for preventing the formation of toxic protein
particles. A limitation of conventional antibodies, however, is
that high concentrations are required to completely inhibit the
formation of toxic protein particles in Alzheimer’s,
Parkinson’s, and other disorders.
To address this limitation, a team of researchers led by
Rensselaer Professor Peter Tessier has
developed a new process for creating antibodies that potently
inhibit formation of toxic protein particles. Conventional
antibodies typically bind to one or two target proteins per
antibody. Antibodies created using Tessier’s method, however,
bind to 10 proteins per antibody. The increased potency enables
the novel antibodies to prevent the formation of toxic protein
particles at unusually low concentrations. This is an important
step toward creating new therapeutic molecules for preventing
diseases such as Alzheimer’s and Parkinson’s.
“It is extremely difficult to get antibodies into the brain.
Less than 5 percent of an injection of antibodies into a
patient’s blood stream will enter the brain. Therefore, we need
to make antibodies as potent as possible so the small fraction
that does enter the brain will completely prevent formation of
toxic protein particles linked to Alzheimer’s and Parkinson’s
disease,” said Tessier, assistant professor in the Howard P. Isermann Department of
Chemical and Biological Engineering at Rensselaer. “Our
strategy for designing antibody inhibitors exploits the same
molecular interactions that cause toxic particle formation, and
the resulting antibodies are more potent inhibitors than
antibodies generated by the immune system.”
Results of the new study, titled “Rational design of potent
domain antibody inhibitors of amyloid fibril assembly,” were
published online last week by the journal Proceedings of
the National Academy of Sciences (PNAS). The study may be
viewed at:
http://www.pnas.org/content/early/2012/11/14/1208797109.abstract
This research was conducted in the laboratories of the Center for Biotechnology and
Interdisciplinary Studies at Rensselaer.
Tessier’s research represents a new way of generating
therapeutic antibodies. Currently, most antibodies are obtained
by exploiting the immune system of rodents. Mice are injected
with a target protein, for example the Alzheimer’s protein, and
the animal’s immune system generates an antibody specific for
the target protein. Tessier’s method is radically different as
it relies on rational design approaches to create antibodies based on properties of the
target proteins.
Along with Tessier, co-authors of the paper are Rensselaer
graduate students Ali Reza Ladiwala, Moumita Bhattacharya,
Joseph Perchiaccaa; Ping Cao and Daniel Raleigh of the
Department of Chemistry at Stony Brook University; Andisheh
Abedini and Ann Marie Schmidt of the Diabetes Research Program
at New York University School of Medicine; and Jobin Varkey and
Ralf Langen of the Zilkha Neurogenetic Institute at the
University of Southern California, Los Angeles.
This study was funded with support from the American Health Assistance
Foundation, the National Science Foundation,
the Pew Charitable Trust, and
the National Institutes of
Health.
For more information on Tessier and his research at
Rensselaer, visit:
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Published
November 30,
2012 |
Contact: Michael Mullaney
Phone: (518) 276-6161
E-mail: mullam@rpi.edu |
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