Michael Pape, president of Nymirum in Ann Arbor, Mich., was awarded an MDA research grant totaling $197,066 over a period of one year to develop drugs to treat type 1 myotonic muscular dystrophy (MMD1, also known as DM1).
MMD1 is due to a gene expansion, which causes a molecule called RNA to accumulate and aggregate (clump together). These RNA aggregates trap a protein called muscleblind, which normally regulates the formation of many other proteins. Loss of muscleblind accounts for many of the features of MMD. One strategy to treat the disease is to prevent the interaction of muscleblind and the RNA aggregates, by blocking the portion of the RNA (called a CUG repeat) where the two bind together.
“Several studies using small molecules and oligonucleotides show that CUG-binding molecules can inhibit muscleblind binding and alleviate the mutation-mediated dysfunctions,” Pape says. “While these studies provide proof of concept, none of the small molecules possesses the required efficacy [effectiveness] and/or drug-like properties for chronic treatment.”
Nymirum has discovered two sets of molecules that appear to have the potential to overcome these limitations. Nymirum will now pursue modifications to these molecules to increase their affinity for the expanded RNA and enhance their therapeutic potential.
Funding for this MDA grant began August 1, 2013.