Les médiateurs pro-résolution de l'inflammation: une nouvelle stratégie thérapeutique pour le traitement de la dystrophie musculaire de Duchenne

 

Nicolas Dumont

Centre de recherche du CHU Sainte-Justine

 

Domaine :  appareil locomoteur et arthrite

Programme chercheurs-boursiers - Junior 1

Concours 2017-2018

Duchenne muscular dystrophy is a severe disease characterized by progressive and irreversible muscle wasting. Dystrophic patients display ambulatory dysfunctions in early childhood that quickly degenerates into respiratory dysfunctions and premature death in young adult. The disease is caused by a genetic mutation in the dystrophin gene, which leads to fragile muscle fiber and muscle degeneration. In normal condition, a population of adult muscle stem cell ensures muscle healing. However, we recently showed that the regenerative capacity of muscle stem cells is impaired in Duchenne muscular dystrophy. Moreover, the chronic degenerative state in dystrophic muscle leads to disorganized and excessive inflammation that further impairs the function of muscle stem cells.

Therefore, muscle wasting observed in Duchenne dystrophy is not only caused by muscle degeneration, it is also attributable to poor muscle healing due to impaired muscle stem cell function. To date, there is no effective treatment for Duchenne muscular dystrophy. Anti-inflammatory glucocorticoids are the only drugs that are able to partially and temporarily slow down muscle wasting. However, their therapeutic impact is limited and they have many side effects that stimulate muscle wasting and reduce the activity of muscle stem cell. Therefore, there is room for improvement and for the development of a more efficient therapy for Duchenne muscular dystrophy.

Our research program study the impact of a new class of therapeutic molecules, the specialized pro-resolving mediators, for the treatment of Duchenne muscular dystrophy. These mediators have potent ability to resolve the inflammation, without the detrimental side effects, and they could directly stimulate muscle stem cell activity and promote muscle regeneration. Restoring muscle stem cell functions in dystrophic patients would preserve their muscle function overtime, improve their quality of life, and ultimately transform this lethal degenerative disease into a manageable condition.