Charles Thornton, professor of neurology at the University of Rochester in New York, was awarded an MDA research grant totaling $308,935 over three years. The funds will help support Thornton's work to expedite the development of effective treatments for type 1 myotonic muscular dystrophy (MMD, also known as DM).
MMD1 is caused by a repeat expansion mutation — an expanded section of DNA — in the DMPK gene, located on chromosome 19. Expanded DNA leads to the creation of expanded and toxic RNA, which causes problems for cells mainly because it traps and disables important proteins. Therefore, an important goal in MMD research is to free these cellular proteins — particularly one called muscleblind 1 or MBNL1 — so that they're able to perform their crucial functions.
One treatment approach that recently has emerged involves the use of small molecules to restore the activity of MBNL proteins, either by increasing their production or by blocking their interactions with toxic RNA. Another approach involves antisense oligonucleotides (AONs) that neutralize RNA toxicity or stimulate the clearance of toxic RNA.
"The model systems that are needed for preclinical testing of these respective approaches are somewhat different," Thornton explains. "Until now, the testing of small molecules has mainly been performed in HSALR transgenic mice, due to advantages of cost and efficiency; however, this model has limitations."
Thornton and colleagues are working to generate new mouse models that better reproduce the muscle weakness and degeneration that are characteristic in human MMD1. In addition, the team plans to design a model that will facilitate the testing of AONs.
Such mouse models could be used in the development and testing of potential new drugs to treat MMD.
Funding for this MDA grant began Aug. 1, 2012.