Novel Small Molecule Inhibitors for the Treatment of Huntington?s Disease
Posted Jun 02 2011 8:00pm
Description of Invention: This technology is a collection of small molecules screened for their ability to prevent or reduce the cytotoxic effects of the protein, Huntingtin. Huntington's disease is a neurodegenerative disorder due to a dominantly acting expansion of a CAG trinucleotide repeat in exon 1 of the Huntington (HTT) gene resulting in production of the altered (mutant) protein Huntingtin, which has a long chain of polyglutamine (poly Q) attached to the exon 1 encoded protein sequence. Clinical and statistical analyses have shown that an increased number of poly Q repetition correlates with the probability of developing the disease, with 36 to 40 being the accepted cut off number for developing the disorder with high probability. It is known that poly Q repetitions impact the physical properties of Huntingtin and cause it to produce aggregates that precipitate and form inclusion bodies, which are toxic to the neuronal cells. The compounds of this invention have been screened multiply in a neuronal cell model of Huntington’s disease containing an HTT with an expanded repeat in exon 1 of 103 Qs for their ability to inhibit cytotoxicity and protein aggregation.
Applications: Treatment of Huntington’s disease.
Development Status: Early development.
Inventors: Juan J Marugan (NHGRI) Joshua G McCoy (NHGRI) Samarjit Patnaik (NHGRI) Steven Titus (NHGRI) Wei Zheng (NHGRI) Noel T Southall (NHGRI) Wenwei Huang (NHGRI)
Collaborative Research Opportunity: The National Center for Translational Therapeutics is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology further. Please contact Ms. Lili Portilla at Lilip@nih.gov for more information.
For Licensing Information Please Contact: Steven Standley Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: sstand@mail.nih.gov Phone: 301-435-4074 Fax: 301-402-0220
Description of Invention:
This technology is a collection of small molecules screened for their ability to prevent or reduce the cytotoxic effects of the protein, Huntingtin. Huntington's disease is a neurodegenerative disorder due to a dominantly acting expansion of a CAG trinucleotide repeat in exon 1 of the Huntington (HTT) gene resulting in production of the altered (mutant) protein Huntingtin, which has a long chain of polyglutamine (poly Q) attached to the exon 1 encoded protein sequence. Clinical and statistical analyses have shown that an increased number of poly Q repetition correlates with the probability of developing the disease, with 36 to 40 being the accepted cut off number for developing the disorder with high probability. It is known that poly Q repetitions impact the physical properties of Huntingtin and cause it to produce aggregates that precipitate and form inclusion bodies, which are toxic to the neuronal cells. The compounds of this invention have been screened multiply in a neuronal cell model of Huntington’s disease containing an HTT with an expanded repeat in exon 1 of 103 Qs for their ability to inhibit cytotoxicity and protein aggregation.
Applications:
Treatment of Huntington’s disease.
Development Status:
Early development.
Inventors:
Juan J Marugan (NHGRI)
Joshua G McCoy (NHGRI)
Samarjit Patnaik (NHGRI)
Steven Titus (NHGRI)
Wei Zheng (NHGRI)
Noel T Southall (NHGRI)
Wenwei Huang (NHGRI)
Patent Status:
HHS, Reference No. E-258-2010/0
US, Application No. 61/388,482 filed 30 Sep 2010
Relevant Publication:
Licensing Status:
Available for licensing.
Collaborative Research Opportunity:
The National Center for Translational Therapeutics is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology further. Please contact Ms. Lili Portilla at Lilip@nih.gov for more information.
For Licensing Information Please Contact:
Steven Standley Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: sstand@mail.nih.gov
Phone: 301-435-4074
Fax: 301-402-0220
Ref No: 2263
Updated: 06/2011