 |
Please Note: The technology listed below is not available to the public at this time. This technology is in the early stage of research and requires further development before it is ready for the marketplace. The VA is currently in the process of identifying potential companies who may be interested in licensing and/or further developing the technology through Cooperative Research and Development Agreements (CRADA). Through cooperative research initiatives such as these, it is our hope and goal that commercial products will be fully developed and made available to benefit veterans and others.
VA TECHNOLOGY OPPORTUNITY BRIEF
The Use of the Histone Deacetylase Inhibitor, Sodium Butyrate, to Promote Neuroprotection, Improve Motor Performance and Reduce Weight Loss in Huntington's Disease
(03-111)
OPPORTUNITY:
The Department of Veterans Affairs (VA) is seeking a commercial partner through a Cooperative Research & Development Agreement (CRADA) to further develop a technology that contains sodium butyrate, a compound that may be used to treat the symptoms of Huntington's disease.TECHNOLOGY OVERVIEW:
Huntington's disease (HD) is a progressive, fatal neurodegenerative disease caused by a mutation in the huntingtin gene. Mutant huntingtin affects gene expression. There is no known cure or treatment that significantly affects disease progression. However, although the sequence of events leading to neuronal death in HD is unknown, it is possible that interference with gene transcription leading to disruption of normal gene expression could be an important step.Gene transcription is regulated by complex interactions between proteins and histones and by the modification of these molecules via acetylation, methylation and phosphorylation. Mutant huntingtin reduces histone acetylation by binding to histone acetyltransferase and can thereby affect gene transcription. Drugs that prevent histone deacetylation can restore transcription in the presence of mutant huntingtin. These drugs, known as histone deacetylase (HDAC) inhibitors, are being studied as cancer chemotherapy agents and include sodium butyrate, phenylbutyrate, trichostatin A, and suberoylanilide hydroxamic acid (SAHA).
The subject technology shows that sodium butyrate, an HDAC inhibitor, significantly enhances survival and reduces neuropathological effects, as well as motor deficits, of HD in R6/2 transgenic mouse models. Sodium butyrate and similar HDAC inhibitors are currently being tested as anticancer drugs due to their inhibitory effects in cell proliferation models.
TECHNICAL MERIT:
The subject technology supports the clinical investigation of sodium butyrate as a viable pharmacological treatment for HD. The technology has been studied extensively in animals and is likely to have a good safety profile in humans. Currently, there are no approved treatments to reduce the effects of HD. Contrary to outcomes noted in studies using SAHA, the subject technology's inventors report that weight loss in R6/2 mice treated with sodium butyrate was delayed in onset. The inventors also demonstrate marked differences in brain pathology in treated R6/2 mice compared to the control R6/2 group.POTENTIAL APPLICATION:
This technology specifically addresses the use of sodium butyrate for the clinical treatment of HD.PATENT STATUS:
A U.S. provisional patent application was filed on February 19, 2004 (60/545,532)
Federal register: June 28, 2004 (Vol. 69, Number 123) p. 36162-36163
US non-provisional patent application filed on February 16, 2005 (11/058,297)FOR MORE INFORMATION CONTACT:
Last Updated - Wednesday, October 26, 2005 2:29 PM
Saleem Sheredos
Program Manager
Technology Transfer Program
Veterans Affairs
Office of Research & Development (12TT)
5th Floor
103 South Gay Street
Baltimore, MD 21202
202-380-5080
Fax 410.962.2141
e-mail: saleem.sheredos@va.gov