2024-01-04 21:59:45
Myotonic dystrophy type 1 (DM1) is a genetic disorder characterized by progressive muscle weakness. It is the most common form of muscular dystrophy. The disease is caused by a genetic mutation that affects an essential process called alternative splicing, important for the proper assembly of proteins throughout the body. This is why the mutations that cause DM1 affect many body systems and cause a wide range of symptoms that are difficult to treat.
There is currently no treatment, despite numerous research efforts. This new study therefore brings great hope.
Japanese researchers have indeed made a first observation of the acceptable safety and tolerability profiles of the antibiotic erythromycin and are optimistic regarding its effectiveness.
Repurposing a common antibiotic to treat muscular dystrophy
In myotonic dystrophy type 1, aberrant RNA transcribed from the mutant DMPK gene leads to the aggregation of splicing regulators. Depletion of intracellular splicing mechanisms leads to splicing abnormalities in different genes. These splicing abnormalities are thought to cause different symptoms of muscular dystrophy. However, erythromycin prevents the aggregation of splicing regulators by binding to abnormal RNAs, thereby restoring splicing regulatory function and reducing symptoms.
An innovative approach: This is a new lead and phase 2 clinical testing of this possible new treatment for myotonic dystrophy type 1. To identify new therapies, the team uses a drug repositioning detection technique, a method in which Medicines already used for a specific purpose are tested for their effects for other indications. The study shows that:
- Erythromycin, a common antibiotic may be effective in the treatment of DM1 due to its ability to reduce splicing abnormalities.
Lead author Dr. Masayuki Nakamori from Osaka University comments on this new Phase II trial data: “Our preclinical trials carried out on cell lines and mouse models provide great hope for the effectiveness of erythromycin in this new indication. This clinical trial carried out on 30 patients suffering from myotonic dystrophy type 1 confirms the safety and tolerability of the treatment, and provides first results of effectiveness.
The test: 6 of 30 patients received a placebo, while 12 received a low dose (500 mg) and 12 received a high dose (800 mg) of erythromycin for 24 weeks. Analysis of splicing markers from patient muscle biopsies reveals:
- in several patients who received erythromycin major improvements which suggest that some patients respond better than others;
- some splicing markers are significantly enhanced with one dose of erythromycin but not the other, also suggesting the importance of dosage.
Despite the small sample size of this trial, the researchers are very optimistic that erythromycin is a promising treatment option.
Phase 2b and 3 trials are already planned.
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