Researchers at the Institute of Myology and I-Stem report encouraging results from metformin, a known antidiabetic agent, for the symptomatic treatment of Steinert myotonic dystrophy. In fact, a phase II trial conducted in 40 patients at the Henri-Mondor AP-HP Hospital shows that, after 48 weeks of treatment at the highest dose, patients treated with metformin (against placebo) gain in motor skills and find a more stable approach. The results of this trial, financed by 1.5 million euros by the AFM-Telethon, are published today in the journal Brain.
Steinert myotonic dystrophy (DM1) is the most common muscle dystrophy in adults. Of genetic origin, its prevalence is estimated at 1 / 8,000, or about 7 to 8,000 patients in France. It affects the muscles, which weaken (dystrophy) and have difficulty to relax after contraction (myotonia) which disrupts the movements (unstable walking for example). It also affects other organs (heart and respiratory system, digestive system, endocrine system and nervous system). To date, this muscular dystrophy does not benefit from any curative treatment.
The results published in Brain are the result of research conducted for several years within I-Stem. Indeed, thanks to the development of cellular models from pluripotent stem cells, in 2011 Cécile Martinat’s team identified new mechanisms at the origin of Steinert’s myotonic dystrophy (Cell Stem Cell – March 31, 2011) . In 2015, Sandrine Baghdoyan, a research engineer at I-Stem, successfully corrects some splice defects in embryonic stem cells and myoblasts from people with DM1 using metformin, a well-known anti-diabetic molecule. identified as effective in this new indication through high-throughput screening (Mol.Therapy – 3 nov 2015).
Based on these results, I-Stem launched a single-phase, double-blind, randomized controlled phase clinical trial in 40 patients, in collaboration with teams from the Henri Mondor APHP Hospital, that of Dr. Guillaume Bassez de the clinical unit of neuromuscular pathology of the Institute of Myology and the reference center for neuromuscular diseases Ile-de-France, and that of the Clinical Investigation Center coordinated by Professor Philippe Le Corvoisier. In this placebo-controlled study, metformin was administered three times daily, orally, with a 4-week increase in dose (up to 3 g / day), followed by 48 weeks at the highest dose. . The evaluation of treatment efficacy was based on the “6-minute walk” test. At the end of the study, after one year of treatment, patients who received metformin gained an average walking distance of about 33 meters on initial performance while the group receiving placebo remained stable (average gain of 10 foot). This motricity, finely analyzed thanks to the Locometryx tool developed by Jean-Yves Hogrel’s laboratory of physiology and neuromuscular evaluation at the Institute of Myology at the Pitié-Salpêtrière hospital AP-HP, is closely linked to the fact that metformin improves the overall posture of patients who, in fact, go from an unstable walking, before treatment, to a straight, faster and therefore more efficient gait”.
These results demonstrate, for the first time, the efficacy of a pharmacological treatment of motor function in Steinert myotonic dystrophy and, to our knowledge, the therapeutic efficacy of a molecule identified on the basis of the modeling of a pathology with pluripotent stem cells.
