Losmapimod is an experimental treatment for facioscapulohumeral muscular dystrophy (FSHD), and it recently received the Orphan Drug designation from the FDA. Not only did it receive this designation, but its creator, Fulcrum Therapeutics, has filed for a U.S. patent. There are currently no therapies for FSHD, making this new designation extremely important. Fulcrum is excited for the current developments and Phase 2b of their clinical trial, which is expected to release its data in the third quarter of 2020.
About Facioscapulohumeral Muscular Dystrophy (FSHD)
Facioscapulohumeral muscular dystrophy (FSHD) is one of the forms of muscular dystrophy, which is a group of diseases that is characterized by the progressive deterioration of muscles. This form of muscular dystrophy sees the weakening of the muscles in the face, around the shoulder blades, and in the upper arms. There are two forms of this disorder: type one and type two. They have the same symptoms and signs, but differ in genetic cause. One of every 20,000 people is affected by FSHD.
Symptoms can vary in severity, and those with milder forms may not notice the effects until later in life. On the other hand, severe forms are noticed in infancy or early childhood. The majority of cases see the onset of symptoms in adolescence.
The first symptom noticed is typically weakness in the facial or shoulder muscles. People will experience difficulty with smiling, whistling, and drinking from straws. They may also have trouble closing their eyes fully during sleep, which can bring other issues like dry eyes. Many people experience more weakness in one half of the face, but the reason for this is unknown. Deterioration of the muscles in the shoulders makes the shoulder blades protrude. Weakness in the upper arms can make it hard to raise one’s arms above their head or throw things.
This weakness will worsen over decades, and other muscles may become affected. The muscles of the legs, abdomen, hips, pelvis, and lower back may also weaken. Rarer symptoms include vision and hearing loss and the weakening of the muscles of the heart and respiratory system.
Changes in chromosome 4 result in FSHD. The end of the chromosome has a portion called D4Z4, and it is hypomethylated in those affected by FSHD. The DUX4 gene is mutated in those with FSHD1. Mutations in the SMCHD1 gene result in FSHD2, but if these changes are present in those with FSHD1, they can increase the severity of symptoms.
FSHD1 is inherited in an autosomal dominant pattern, but some cases see sporadic mutations. The second form of this disorder is caused by a digenic pattern, which means that they must inherit one copy of the mutated SMCHD1 gene and one copy of a ‘permissive’ chromosome 4.
A clinical examination, finding of characteristic symptoms, and evaluation of family history is usually enough for a diagnosis. Other tests may be performed to confirm, such as blood tests, EMGs, muscle biopsies, and genetic testing. Once one has received a diagnosis, treatment is symptomatic. Physical and speech therapy are helpful, and walking aids may be necessary. Surgery is an option to correct issues with shoulder blades. Testing should also occur for the eyes and ears to ensure that there is no loss of those senses.
Losmapimod is a selective p38α/β mitogen activated protein kinase inhibitor. This inhibitor reduces the effects of the DUX4 gene, which causes FSHD1. The current clinical trial is the first time losmapimod has been used for the treatment of any form of muscular dystrophy, but it has been indicated in the treatment of other disorders and has been studied in over 3,500 subjects. No safety issues were found in any other trial, making this treatment a viable option for many.
About the Clinical Trial
Data will be released from Phase 2b of this trial in the third quarter of 2020. Phase 1 of the trial has already been completed, and results showed that losmapimod was well-tolerated.
Fulcrum Therapeutics is excited for their new designation and patent, and they hope that these things will allow them to improve and continue their work.
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