Ricerc@Sapienza

Statins are a group of drugs that reduce the levels of triglycerides and cholesterol in blood by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). About 5-20% of patients do not tolerate the side effects of statins, resulting in discontinuation of therapy. Patients commonly report dose-dependent self-limited musculoskeletal sign and symptoms ranging from asymptomatic increase of serum creatin kinase (CK) to necrotizing myopathy. A small number of patients (0.002-0.003%), develop a progressive, immuno-mediated necrotizing myopathy (IMNM). The latter is characterized by progressive muscle weakness, elevated muscle enzymes, and progression of symptoms and signs despite discontinuation of statins. The IMNM has been associated with the presence of autoantibodies directed against the catalytic domain of HMGCR.
The present project aims to review morphologic and immunoistochemical features of muscle from 24 consecutive patients who underwent muscle biopsy because of clinical suspicion of statin-related myopathy and 22 patients with diagnosis of IMNM not related to statin. The goal is to highlight morphologic markers useful to differentiate statin-related myopathy from other form of skeletal muscle disease and to distinguish morphologic features related to statin direct toxic effects versus immune-mediate damage.
Moreover, to improve the diagnostic utility of muscle biopsy we aim to test antibodies against HMGCR to verify if muscle from patients with statin-related IMNM show up-regulation as compared with muscle with IMNM due to other causes. Detection of HMGCR overexpression on muscle from patients with necrotizing myopathy and statin exposure might facilitate diagnosis of statin-related IMNM on muscle biopsy.