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Staging system in ALS shows potential tracks of disease progression, Penn study finds
Date:6/19/2013

PHILADELPHIA - The motor neuron disease Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, progresses in a stepwise, sequential pattern which can be classified into four distinct stages, report pathologists with the Perelman School of Medicine at the University of Pennsylvania in the Annals of Neurology. This post-mortem staging of ALS brain and spinal cord tissues shows, for the first time, how the fatal degenerative disease may progress from one starting point in the central nervous system to other regions of brain and spinal cord. As evidence mounts showing that other neurodegenerative diseases, such as Alzheimer's and Parkinson's, transmit disease-specific pathological proteins from cell-to-cell within the interconnected brain regions of affected individuals, this study suggests that a similar transmission process may be spreading toxic TDP-43 proteins and damaging motor neurons in the brain and spinal cord of ALS patients.

"Researchers at Penn and beyond can now start to investigate and try to confirm this transmission process in ALS, by looking for cell to cell transmission of TDP-43 in models of ALS," said senior author John Trojanowski, MD, PhD, director of the Penn Institute on Aging and professor of Pathology and Laboratory Medicine at Penn. "If this transmission process can be identified and understood in ALS, this opens a new pathway for treatments, such as immunotherapies that could interrupt or block damaged and destructive proteins from corrupting other cells, thus halting the spread of disease."

Researchers examined 76 autopsies of patients with ALS, measured pathological TPD-43 distribution and concentration in the nervous system, and were able to map out four distinct stages to assess the disease and burden of pathology.

  • In stage 1, TDP-43 pathology was found within the primary motor cortex, as well as neurons in the spinal cord and nerves in the brainstem involved with swall
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Contact: Kim Menard
kim.menard@uphs.upenn.edu
215-662-6183
University of Pennsylvania School of Medicine
Source:Eurekalert

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