First Mouse Model for Multiple System Atrophy
Points to New Treatment Targets for Brain Diseases
(Philadelphia, PA) - A newly developed animal model for Multiple System
Atrophy (MSA) - a collection of neurodegenerative disorders once thought
to be three separate diseases - sheds new light on this little-studied
brain disease, according to research from investigators at the University
of Pennsylvania School of Medicine.
Virginia M.-Y. Lee, PhD, Director of Penn’s Center
for Neurodegenerative Disease Research, and colleagues demonstrated that
the mice showed symptoms similar to human MSA. These include an accumulation
of a protein called a-synuclein in oligodendrocytes - cells that produce
the protective myelin sheath that covers axons. This protein accumulation
disables oligodendrocytes, leading to a loss of the sheath on neurons
and eventually nerve-cell malfunction and death. The mice also showed
slowly progressive problems with their motor skills associated with the
nerve-cell damage. Neurons are important in transmitting signals and in
maintaining learning and memory.
“The uniqueness of this disease is that, unlike most of the neurodegenerative
diseases, which affect neurons primarily and oligodendrocytes secondarily,
this is the other way around,” says Lee. In fact, there is growing
evidence that non-neuronal cells also play a role in amyloid deposits
in Alzheimer’s disease and amyotrophic lateral sclerosis (ALS) mouse
models. Lee and colleagues report their findings in the March 24, 2005
issue of Neuron.
MSA is so named because it affects multiple parts of the nervous system.
Initially MSA was given three names, based on the symptoms physicians
had observed. However, when they closely examined patients’ pathology,
the disorders seemed related, based on the a-synuclein proteins in cells.
In the clinic, many patients with MSA present with symptoms similar to
Parkinson’s disease (PD), and MSA has been misdiagnosed as such.
Collectively, MSA now includes three related disorders characterized by
their most prominent symptoms: olivopontocerebellar atrophy, which affects
balance, coordination, and speech; striatonigral degeneration, the closest
to Parkinson’s disease because of slow movement and stiff muscles;
and Shy-Drager syndrome, which involves altered bowel, bladder, and blood-pressure
control. Other general symptoms include dizziness, impaired speech, breathing
and swallowing difficulties, and blurred vision. Most patients develop
dementia late in the course of the disease, which is usually diagnosed
in people over 50.
Currently there is no specific drug to treat the myelin and nerve damage
caused by the protein inclusions. Parkinson’s disease drugs and
others are used to alleviate early symptoms. “With this animal model,
we now can plan tests of potential therapies for Multiple System Atrophy
as part of our drug discovery program for Parkinson’s disease, MSA,
and related disorders,” says Lee.
The study was funded in part by the National Institutes of Health. Ikuru
Yazawa, Benoit I. Giasson, Ryogen Sasaki, Bin Zhang, Sonali Joyce, Kunihuro
Uryu, and John Q. Trojanowski, all from Penn, are study co-authors. The
authors report no conflicts of interests related to this research.
For more information see http://www.ninds.nih.gov/disorders/msa/msa.htm.
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