Repurposing of Trimetazidine for amyotrophic lateral sclerosis: A study in SOD1G93Amice

• DOI: 10.1111/bph.15738
• Publication Date: 2021-11-16T09:51:57Z
• Authors: Silvia Scaricamazza; Illari Salvatori; Susanna Amadio; Valentina Nesci; Alessio Torcinaro; Giacomo Giacovazzo; Aniello Primiano; Michela Gloriani; Niccolò Candelise; Luisa Pieroni; Jean‐Philippe Loe...; Frederique Renè; Cyril Quessada; Tesfaye W. Tefera; Hao Wang; Frederik J. Steyn; Shyuan T. Ngo; Gabriella Dobrowolny; Elisa Lepore; Andrea Urbani; Antonio Musarò; Cinzia Volonté; Elisabetta Ferraro; Roberto Coccurello; Cristiana Valle; Alberto Ferri
• Keywords: Trimetazidine

Background and Purpose Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by the degeneration of upper lower motor neurons, progressive wasting paralysis voluntary muscles is currently incurable. Although considered to be pure neuron disease, increasing evidence indicates that sole protection neurons single targeted drug not sufficient improve pathological phenotype. We therefore evaluated therapeutic potential multi‐target used treatment coronary artery trimetazidine, in SOD1 G93A mice. Experimental Approach As metabolic modulator, trimetazidine improves glucose metabolism. Furthermore, enhances mitochondrial metabolism promotes nerve regeneration, exerting an anti‐inflammatory antioxidant effect. orally treated mice with solubilized drinking water at dose 20 mg kg −1 , from onset. assessed impact on progression studying parameters, grip strength histological alterations skeletal muscle, peripheral nerves spinal cord. Key Results Trimetazidine administration delays function decline, muscle performance metabolism, significantly extends overall survival (increased median 16 days 12.5 for male female respectively). Moreover, prevents neuromuscular junctions, attenuates loss reduces neuroinflammation cord nerves. Conclusion Implications In mice, effect underpinned its action