An estimated 80% or more of people with myotonic dystrophy type 1 (DM1) struggle with severe fatigue and excessive daytime sleepiness (EDS). While most people consider myotonia (inability to contract voluntary muscles) and muscle weakness to be the most debilitating DM1 symptoms, those affected tend to report that fatigue and EDS can be just as challenging to handle.
Pitolisant, marketed as Wakix, is currently approved to treat EDS and cataplexy in adults with narcolepsy, as well as EDS in children with narcolepsy ages six or older. The drug works by targeting histamine H3 receptors and regulating histamine release. Histamine, a neurotransmitter, plays a role in wakefulness and alertness. When your body promotes histamine release, it reduces fatigue. So, researchers wondered, could pitolisant offer a potential therapeutic benefit in DM1?
Evaluating Pitolisant
An article in Sleep Review explains that Harmony Biosciences ran a Phase 2 signal detection study to evaluate pitolisant for people with DM1. 25 individuals enrolled. These individuals were split into three groups. The first group received the placebo, the second a low dose of pitolisant, and the third a high dose of pitolisant. Researchers found that:
- Both high- and low-dose pitolisant improved fatigue and excessive daytime sleepiness. Improvement was more significant in the higher-dose group. However, it’s important to note that this was just a signal detection study. While the results were promising, they cannot show statistical significance.
- Pitolisant showed consistency in safety and tolerability compared to its known safety profile.
Moving forward, Harmony Biosciences plans to launch further studies (including a Phase 3 study) on pitolisant for DM1.
About Myotonic Dystrophy type 1 (DM1)
There are two major forms of myotonic dystrophy, a rare multi-system genetic disorder. Myotonic dystrophy type 1 (DM1), caused by an abnormally expanded section on chromosome 19 (DMPK), typically causes muscle weakness in the lower legs, hands, neck, and face. Alternately, myotonic dystrophy type 2 (DM2) is caused by CNBP gene mutations; this form is milder in nature, with muscle weakness affecting the neck, shoulders, hips, and elbows.
Since the pitolisant study was performed in the DM1 space, that’s what we’ll focus on today. DM1 can be present at birth (congenital DM1), in adolescence (juvenile DM1), or in adulthood. The adult form is most common and manifests, usually, in someone’s 30s. Signs and symptoms of myotonic dystrophy type 1 can vary, but may include:
- Cataracts
- Constipation or gallstones due to gastrointestinal tract weakness
- Drooping eyelids
- Slurred speech
- Myotonia
- Muscle pain
- Pregnancy and labor complications due to abnormal uterine muscles
- Fatigue
- Abnormal heart rhythm due to heart muscle weakness
- Early baldness/an increased likelihood of baldness
- Difficulty breathing
- Hypogonadism
This is not an exhaustive list of symptoms.
Currently, no cure exists for myotonic dystrophy. Doctors choose care plans based on each patient’s specific needs.
If you have myotonic dystrophy and are looking for support, the Myotonic Dystrophy Foundation is here for you.
