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Methods for the Treatment of Parkinson's Disease and Other alpha-synucleinopathies

Posted Jun 13 2010 5:00pm

Description of Invention:
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. During the course of the disease, proteinaceous cytoplasmic inclusions known as Lewy bodies appear in the dopaminergic neurons. Several lines of evidence point to a key role for alpha-synuclein, a major constituent of Lewy bodies, in the pathogenesis of these disorders. In particular, the aggregation of this protein is believed to be deleterious to neurons. These inventors have now discovered that transglutaminase 2, also referred to as tissue transglutaminase, catalyzes alpha-synuclein cross-linking in vitro and in cultured cells. Evidence for the activity of this enzyme is also provided within the Lewy bodies in Parkinson's patients. The present invention provides novel methods for the treatment of Parkinson's disease and other alpha-synucleinopathies with inhibitors of transglutaminase, which can inhibit aggregation of alpha-synuclein. Also provided are screening assays for novel inhibitors of transglutaminase that may be used in the treatment of Parkinson's disease and other alpha-synucleinopathies. Further information may be found in Junn et al., PNAS 2003 100(4): 2047-2052.

M Maral M Mouradian (NINDS)

Patent Status:
HHS, Reference No. E-091-2003/0
US, Application No. 60/444,563 filed 02 Feb 2003

Central Nervous System
Central Nervous System - Therapeutics
Central Nervous System - Other
In-vitro Data

For Additional Information Please Contact:
Charlene Sydnor Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Phone: 301-435-4689
Fax: 301-402-0220

Ref No: 863

Updated: 06/2010

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