Methods for Preparing Multivalent RNA-Targeting Ligands with Specific Application Towards Targeting the (CUG)n Oligomers that Cause Myotonic Dystrophy

University at Buffalo - The State University of New York
posted on 10/20/2009

Trinucleotide repeat disorders are genetic disorders caused by extended stretches of DNA encoded with the same trinucleotide sequence repeated many times. Some of the most notable trinucleotide repeat disorders include Myotonic Dystrophy, Fragile X, Huntington's, and Friedreich's ataxia. Myotonic Dystrophy (DM) is the most common form of Muscular Dystrophy, an inherited condition estimated to affect 1 in 8,000 individuals. DM is characterized as a multi-system disorder with clinical features affecting the skeletal muscle the heart, the eye and the endocrine system. The defect in DM is believed to be an amplified trinucleotide (CTG) repeat located in the 3'-untranslated region of the dystrophia myotonica-protein kinase gene (DMPK). The presence of these 5'CUG/3'GUC mRNA repeats results in its binding to muscleblind protein, thereby preventing normal muscle function. Medicinal chemists at the University at Buffalo have developed a series of unique compositions that target and bind the mRNA repeat. By targeting the mRNA repeat, these compositions prevent binding of the mRNA to muscleblind protein, thus restoring normal muscle function to the patient. Unlike competing technologies, such as antisense and gene silencing techniques, these multivalent, small molecule compositions are not likely to face the same delivery and stability hurdles, making them ideal candidates for development as therapeutics for DM.

Detailed Description

Trinucleotide repeat disorders are genetic disorders caused by extended stretches of DNA encoded with the same trinucleotide sequence repeated many times. Some of the most notable trinucleotide repeat disorders include Myotonic Dystrophy, Fragile X, Huntington's, and Friedreich's ataxia. Myotonic Dystrophy (DM) is the most common form of Muscular Dystrophy, an inherited condition estimated to affect 1 in 8,000 individuals. DM is characterized as a multi-system disorder with clinical features affecting the skeletal muscle the heart, the eye and the endocrine system. The defect in DM is believed to be an amplified trinucleotide (CTG) repeat located in the 3'-untranslated region of the dystrophia myotonica-protein kinase gene (DMPK). The presence of these 5'CUG/3'GUC mRNA repeats results in its binding to muscleblind protein, thereby preventing normal muscle function. Medicinal chemists at the University at Buffalo have developed a series of unique compositions that target and bind the mRNA repeat. By targeting the mRNA repeat, these compositions prevent binding of the mRNA to muscleblind protein, thus restoring normal muscle function to the patient. Unlike competing technologies, such as antisense and gene silencing techniques, these multivalent, small molecule compositions are not likely to face the same delivery and stability hurdles, making them ideal candidates for development as therapeutics for DM.

File Number: 6170

Disease: Genetic Diseases and Dysmorphic Syndromes

Other Information: Principal Investigator: Mathew Disney

This innovation currently is not available for online licensing. Please contact Tim Dee at University at Buffalo - The State University of New York for more information.

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