Is a Therapy for Congenital Myotonic Dystrophy Type 1 in Sight?

Lubov Timchenko, PhD, has dedicated more than 15 years of her professional career to understanding the causes of congenital and adult myotonic dystrophy type 1 (DM1). Now, she and her colleagues at Cincinnati Children's are closer to developing clinical trials in adult and congenital DM1 using the inhibitors of glycogen synthase kinase-3 (GSK3). If successful, this could represent a promising breakthrough in treating children with this devastating disease, whose symptoms can include hypotonia with severe muscle weakness.

Dr. Timchenko recently joined Cincinnati Children's, where she continues the research she began at Baylor College of Medicine. Three years ago, she and her colleagues determined that the enzyme GSK3ß, when inhibited, can reduce muscle myopathy, myotonia and weakness in mice that have the mutation for DM1 (read the study). A year later, they showed that correction of GSK3ß activity in the mouse model reduces DM1 muscle atrophy.

Now, at Cincinnati Children's, Dr. Timchenko's lab is working toward application of the inhibitors of GSK3 in a clinical trial for DM1. This therapeutic approach has a potential to reduce the progression of DM1. “The inhibitors of GSK3 might be especially important for pediatric patients who have the mutation for DM1, because we found that the inhibitors of GSK3 improve muscle strength in young mice that carry the mutation," Dr. Timchenko says. “Our hope is that by using these inhibitors in pediatric patients, we can achieve similar results."

Dr. Timchenko believes that clinical trials using GSK3 inhibitors in patients with the adult form of DM1 might begin in a few years. But first, her lab is completing animal studies to test different inhibitors in mice in order to identify their potential and establish safe doses for patients. She and her team also are working to determine if GSK3 inhibitors are beneficial for children with congenital DM1.

To learn more, contact Dr. Luba Timchenko.