Compounds Target RNA Linked to Type of Muscular Dystrophy

BUFFALO, N.Y. -- A University at Buffalo medicinal chemist has identified compounds to target a ribonucleic acid (RNA) that causes a form of muscular dystrophy called myotonic dystrophy, or DM.

As with all forms of muscular dystrophy, no treatment currently exists for DM, which is characterized by the inability of muscles to relax at will. Cases of the disease can vary widely in severity based on the severity of the RNA defect and it frequently is diagnosed in the adult years.

According to Matthew Disney, Ph.D., whose research focuses on developing a chemical code for targeting RNA with small molecules, DM belongs to a class of diseases called triplet repeat disorders in which the genetic code has an abnormal repetition of three letters of DNA.

"The DNA with the abnormal triplet repeats is made into a defective RNA that forms an unnatural structure that binds to a protein important in muscle function," explains Disney, assistant professor in the Department of Chemistry in the UB College of Arts and Sciences. "It is this RNA-protein interaction that causes the disease."

Disney in 2006 was one of just seven scientists in New York State to be awarded a $200,000 James D. Watson Investigator grant from the New York State Office of Science, Technology and Academic Research. He is using the award for work to target some of these RNA structures with small molecules developed in his lab at UB.

RNA, DNA's chemical cousin, is a template for protein synthesis, which orchestrates protein-building, catalyzes chemical reactions and performs many other essential roles in cells.

Mutations in RNA can alter expression of proteins that can lead to cancer, sickle cell anemia and other diseases, one of which is DM.

Initial research efforts will be focused on validating Disney's approach for designing compounds to target RNA structures, as well as confirming that the DM RNA target is a viable one for treating this disease.

If the early research is successful, then Disney and his colleagues will tackle the much more challenging issue of developing their compound into a viable pharmaceutical treatment.

In addition to the NYSTAR award and funding from the Camille & Henry Dreyfus Foundation, Disney is supported by, and is a member of, UB's New York State Center of Excellence in Bioinformatics and Life Sciences.

A UB faculty member since 2005, Disney graduated from the University of Maryland and earned a master's in chemistry and a doctorate in biophysical chemistry from the University of Rochester. He lives in Williamsville.

The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York.