May 9, 2003
Boston Cure Project
Dr. Marie Filbin, Distinguished Professor of Biology at City University of New York (and now a member of the Boston Cure Project Scientific Advisory Board) is interested in finding out what prevents the adult central nervous system from regenerating after injury -- a topic relevant to MS since axonal degeneration is a critical feature of the disease.
What Dr. Filbin has found is that certain components of myelin, such
as MAG (myelin-associated glycoprotein), actually inhibit axonal regeneration.
She has found that the inhibitory effect of MAG or myelin on neuron growth
depends on the age of the neurons -- young ones will grow and extend neurites
in the presence of myelin, whereas older ones will not. In addition to
figuring out the exact mechanisms by which this inhibition occurs, she
is also looking for ways to keep it from happening so that regeneration
can take place despite the presence of myelin.
Dr. Filbin described several of the experiments that she and her colleagues and staff have conducted to track down a way to block the inhibitory effects of myelin on neural regeneration. They found that cyclic adenosine monophosphate (cyclic AMP, or cAMP) and certain neurotrophins (such as brain-derived neurotrophic factor, or BDNF) can block or prevent MAG inhibition. Further study of cAMP showed that it appears to act by increasing production of certain proteins such as interleukin-6 and arginase-1. Both of these were then demonstrated to block MAG inhibition. Now Dr. Filbin and her crew are investigating exactly what these compounds are doing that permits regeneration (for instance, Arg-1 appears to stimulate production of polyamines, so the next logical question is what do these polyamines do, and so on).
Jumping back to the cAMP step, Dr. Filbin's team is also studying the effects of an antidepressant drug called Rolipram that protects cAMP from being broken down in the body. The thought is that this drug, by preserving cAMP, will therefore increase levels of IL-6 and Arg-1, etc., thereby increasing levels of key polyamines and other compounds, etc. and thereby permitting damaged axons to grow even in the presence of myelin. Interestingly, Rolipram is currently in trials for MS because of its potential to dampen the immune system. Perhaps it will have beneficial effects in the CNS as well?
Dr. Filbin cautioned that allowing axons to grow is only one step of
several needed to restore CNS function in damaged areas. Other required
steps include prevention of the scar tissue that is formed by astrocytes
in the weeks after injury, induction of axonal growth in the right direction
and to the right place, formation of a myelin sheath around the new axon
by oligodendrocytes, etc. But with sufficient progress in each of these
areas combined, maybe someday scientists can help reverse some of the axonal
damage caused by MS and thereby slow down or stop the accumulation of disability
experienced by people with MS.
Copyright © 2003, Boston Cure Project