Spermidine as new candidate for the treatment of COL6 myopathies (SpeCTre-COL6)

Our research group has been studying for years human muscular dystrophies due to the lack of collagen VI (COL6), including the Ullrich congenital dystrophy (UD) and Bethlem myopathy (BM). We contributed to discover some pathological mechanisms that characterize these diseases and investigated potential therapies able to attenuate the symptoms and muscle defects. Now, we want to evaluate the potential of a natural molecule called spermidine, soluble in water and already present in many foods, which gives a cellular response called autophagy. Autophagy represents the "waste disposal company" of the cell: if it does not work well, the waste accumulates and damages the cell. Autophagy is indeed altered in UD and BM patients and in the COL6-knockout murine model that mimics these pathologies, and its reactivation is beneficial and improves the state of the diseased muscle. This preclinical project aims to test spermidine efficacy on UD and BM cells and in mice lacking COL6. In particular: (a) we will characterize autophagy defects in cells obtained from skin and muscle of COL6 patients; (b) we will supply spermidine to mice in drinking water, to test its ability to recover muscle strength due to the absence of COL6; (c) we will investigate which biological parameters are measurable in response to spermidine treatments, both in the blood and in the cells obtained from these animals and from UD and BM patients. Our results will provide the information needed to start the design of clinical trials for COL6 patients based on the use of a nutraceutical potentially free of side effects. Furthermore, to increase patients' well-being, we will try to identify new tools for monitoring therapeutic responses for example in blood or in skin samples, thus reducing the use of invasive interventions such as muscle biopsies.