Advancing Novel Treatments for Patients with Muscle Disease

Standard of Care / Unmet Need

DM1 is a progressive multisystem disorder. Weakness and myotonia (inability to relax muscles) are often the most prominent symptoms, especially in the lower legs, hands, neck and face. Upper extremity disability and difficulty walking are typical. Patients commonly experience other symptoms, including cognitive problems, daytime sleepiness and sleep disturbance, arrhythmias, respiratory abnormalities, and diabetes. The type and severity of manifestations vary greatly between individuals, ranging from more common adult-onset forms with varying degrees of weakness, to child-onset and congenital forms that are more severe and sometimes life-threatening. This variability is partially accounted for by the number of repeats, which can number in the hundreds or thousands, compared to less than 35 in healthy individuals.

DM1 is caused by impaired RNA processing. Patients with DM1 have an increased number of CTG triplet repeats in the myotonic dystrophy protein kinase gene (DMPK). Transcribed CUG repeats form complex structures (hairpin loops) that bind to Muscleblind like splicing regulator (MBNL) proteins, trapping it in nuclei and preventing it from properly regulating the splicing of mRNA for many other genes, causing the spectrum of symptoms affecting patients with DM1.

Presently there are no approved disease-modifying medicines for DM1. Supportive treatments include physical therapy, braces, walking assistive devices for muscle symptoms, and other medications and devices for myotonia and cardiac, respiratory and endocrinologic manifestations.

Our Approach

Kate Therapeutics is evaluating ways to reduce toxic CUG repeats and restore activity of MBNL in muscle.

DM1 Resources

Disease State Information

Advocacy Organizations