F088 Skeletal muscle atrophy in Huntington disease and protective effects of ghrelin

<h3>Background</h3> Skeletal muscle wasting alongside central pathology is a well-recognized phenomenon seen in patients with Huntington´s disease (HD) and in HD mouse models. HD muscle atrophy progresses with disease and affects prognosis and quality of life. Satellite cells, progenitors of mature skeletal muscle fibres, are essential for the proliferation, differentiation, and repair of muscle tissue in response to muscle injury or exercise. Ghrelin, a gut peptide-hormone, plays an important role in regulating energy metabolism and has been shown to rescue R6/2 mouse catabolism. <h3>Aim</h3> In this study, we investigated the effect of HTT CAG repeat expansion and the impact of ghrelin treatment, on proliferation and differentiation capacity of satellite cells. We utilized the R6/2 mouse model and C2C12 murine myoblasts transfected with HTT-Q74 or HTT-Q23. <h3>Methods</h3> We assessed mutant HTT expression and ghrelin effects on myocytes using real-time qPCR, Western blot, and histological analysis. <h3>Results</h3> We found a significant reduction in myofiber diameter in differentiated satellite cells from skeletal muscle (gastrocnemius) cultured from R6/2 mice compared to WT mice and that ghrelin exerted protective effects. <h3>Conclusion</h3> In addition to known degenerative effects of mutant HTT in skeletal muscle fibres, mutant HTT may have a deleterious impact on the proliferation and/or differentiation processes of muscle progenitors. Our results suggest that ghrelin treatment at the early stages of the disease could potentially provide a novel therapeutic target for delaying muscle atrophy in HD. Taken together, further studies evaluating the underlying mechanism are warranted.