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First Mouse Model For Multiple System Atrophy Points To New Treatment Targets For Brain Diseases

Date:
April 1, 2005
Source:
University Of Pennsylvania Medical Center
Summary:
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.

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.


Story Source:

The above story is based on materials provided by University Of Pennsylvania Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Pennsylvania Medical Center. "First Mouse Model For Multiple System Atrophy Points To New Treatment Targets For Brain Diseases." ScienceDaily. ScienceDaily, 1 April 2005. <www.sciencedaily.com/releases/2005/03/050329131521.htm>.
University Of Pennsylvania Medical Center. (2005, April 1). First Mouse Model For Multiple System Atrophy Points To New Treatment Targets For Brain Diseases. ScienceDaily. Retrieved August 22, 2014 from www.sciencedaily.com/releases/2005/03/050329131521.htm
University Of Pennsylvania Medical Center. "First Mouse Model For Multiple System Atrophy Points To New Treatment Targets For Brain Diseases." ScienceDaily. www.sciencedaily.com/releases/2005/03/050329131521.htm (accessed August 22, 2014).

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