Last week, biotechnology company Triplet Therapeutics announced their participation in END-DM1, a natural history study to learn more about myotonic dystrophy. There are two major forms of myotonic dystrophy, a rare genetic disease which causes progressive muscle loss and weakness. First, type 1 results from an abnormal DMPK gene mutation. This causes CTG nucleotide repeats, which lead to a variety of symptoms. Additionally, these repeats expand over time, causing disease progression. Traditionally, type 1 myotonic dystrophy is more severe. Muscle weakness impacts the legs, hands, neck, and face.
Next, type 2 results from a ZNF9 gene mutation. This form is usually somewhat milder, and muscles affected are usually the neck, hips, shoulders, and elbows. In both cases, myotonic dystrophy usually occurs in adulthood.
Symptoms include:
- Prolonged muscle contractions
- Cataracts
- Difficulty swallowing
- Voluntary muscle weakness
- Abnormal heart rhythm
- Speech, hearing, and vision problems
- Constipation
- Heart, chest, lung, and other muscle weakness
- Difficulty breathing
- Gallstones
- Apathy
- Learning disabilities
- Pregnancy complications
Read more on myotonic dystrophy.
END-DM1 for Myotonic Dystrophy
In this large study, researchers will look to supplement their knowledge on myotonic dystrophy type 1 (DM1), as well as develop potential biomarkers, clinical approaches, diagnostic criteria, and treatments. The focus is to identify potential therapeutic targets for genetic disorders with nucleotide repeats. For example, beyond DM1, Triplet Therapeutics is also searching for a Huntington’s disease treatment in the SHIELD HD study.
Unlike a clinical trial, END-DM1 is a natural history study. According to a draft guidance document from the FDA, a natural history study is:
a preplanned observational study intended to track the course of [a] disease. Its purpose is to identify demographic, genetic, environmental, and other variables (e.g., treatment modalities, concomitant medications) that correlate with the disease’s development and outcomes.
Generally, these studies look at current patients with a disease, their standard of care, care emergencies, and disease manifestations. Rather than examining treatment efficacy, natural history studies look at disease progression without any external interventions.
Over a 4-year period, END-DM1 will examine around 700 patients aged 18 to 70 with DM1. However, the study is currently suspended due to COVID-19.
