MMD Research: Drug Development?

The identification of small molecules that can block the genetic defect that causes type 1 myotonic dystrophy (MMD1, or DM1) may be the first step toward developing a new drug treatment for the disease, say researchers at the University of Rochester (N.Y.) Medical Center (URMC).

The abnormality that underlies MMD1 is a stretch of genetic material derived from DNA on chromosome 19 that contains more than the usual number of a repeating chemical sequence known as a CUG (cytosine, uracil, guanine) triplet repeat.

A major effect of the CUG triplet repeats in RNA (genetic instructions derived from DNA) is the entrapment and disabling of a protein called MBNL1, also known as muscleblind 1. Normally, MBNL1 helps build cellular channels for chloride ions, which are essential for muscle function. But when it's stuck to CUG triplet repeats, it can't play this role.

Cell Nucleus
In MMD1, extra-long strands of genetic material called RNA trap a protein called MBNL1. Scientists say they can prevent this interaction in the laboratory.

The newly identified small molecules prevent MBNL1 from becoming ensnared in the CUG triplet repeat trap, freeing it to do its usual job helping muscle function.

The molecules potentially could be developed into a therapy that would prevent the toxic interaction between MBNL1 and CUG triplet repeats and treat the disease.

A research team led by chemist Benjamin Miller published its findings online Nov. 7 in the Journal of the American Chemical Society. The team included neurologist Charles Thornton, who co-directs the MDA-supported clinic at URMC and who has received MDA funding for MMD1 research.

"This is an important first step toward developing a drug treatment for myotonic dystrophy," Thornton said. "The message from our patients is loud and clear -- push this forward as fast as possible."

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