MFN2 agonists reverse mitochondrial defects in preclinical models of Charcot-Marie-Tooth disease type 2A

• DOI: 10.1126/science.aao1785
• Publication Date: 2018-05-07T19:16:17Z
• Authors: Agostinho G. Rocha; Antonietta Franco; Andrzej M. Krezel; Jeanne M. Rumsey; Justin M. Alberti; William C. Knight; Nikolaos Biris; Emmanouil Zachari...; James W. Janetka; Robert H. Baloh; Richard N. Kitsis; Daria Mochly-Rosen; R. Reid Townsend; Evripidis Gavathi...; Gerald W. Dorn
• Keywords: 0303 health sciences; Mitochondrial Diseases; Glutamine; Arginine; Sciatic Nerve; Axons; GTP Phosphohydrolases; Mitochondria; 3. Good health; Mice, Inbred C57BL; Mitochondrial Proteins; Disease Models, Animal; Mice; 03 medical and health sciences; Methionine; Amino Acid Substitution; Charcot-Marie-Tooth Disease; Drug Design; Animals; Humans; Phosphorylation; Oligopeptides; Protein Kinases

An innovative approach for a rare disease

Charcot-Marie-Tooth disease type 2A (CMT2A) is a rare, inherited neurodegenerative condition. Affected individuals develop severe progressive muscle weakness, motor deficits, and peripheral neuropathy. Although defects in the gene encoding mitofusin 2 (MFN2) are known to cause CMT2A, the disease remains incurable. Rocha et al. identified specific MFN2 residues contributing to the disease and developed a class of MFN2-agonist drugs. The small molecules restored mitochondrial fusion and activity in the sciatic nerves of mice; they may also help in other diseases linked to mitochondrial trafficking.

Science , this issue p. 336