Clinical, molecular and pathogenetic studies of Neutral Lipid Storage Disease (NLSD)

The Neutral Lipid Storage Disease represents a recently recognized genetic disorder. This comprises a group of rare syndromes caused by an abnormal accumulation of lipids in the cells which determines muscle, heart and skin problems. The genetic causes of NLSD have been discovered, but its clinical characteristics as well as natural history have not been fully defined. For this reason Neutral Lipid Storage Disease may go sometime underdiagnosed and many doctors have difficulties in managing affected individuals. We know that one of these syndromes determines a severe, irreversible disability due to muscle damage, the mechanisms by which patients develop this complication are totally unknown. Also it has been reported that affected individuals accumulate lipids also in other organs, including heart and liver, but the clinical implications of this phenomenon are not clearly defined. Therefore we have designed this project to get more insight into the clinical complications and the natural history of this disease. As an animal model mimicking the human disease is available, we plan also to use this model to get more information in to the mechanisms that cause the muscle disease in NLSD patients. NLSD has no cure. Then, we will use cells obtained from patients and the mouse model to evaluate the benefit of three different drugs which have been demonstrated to be are able to stimulate cellular lipid catabolism and muscle function. The results of this project will improve the ability to manage NLSD and might also provide useful information to develop a therapy for this, otherwise incurable, diseases.