Thymidine kinase 2 deficiency (TK2d) is a rare mitochondrial disease due to mutations in the TK2 gene (TK2). Deficiency of TK2 enzyme causes depletion and multiple deletions of mitochondrial DNA that lead to progressive muscle weakness that begins in infancy through adulthood. Our studies of a mouse model of TK2d have indicated that deoxynucleosides can be effective in bypassing the enzymatic defect. Ongoing expanded access treatment and clinical trials with deoxynucleosides for TK2d are being conducted internationally.
Dr. Michio Hirano is a Professor of Neurology and Chief of the Division of Neuromuscular Medicine at Columbia University Medical Center. For over 20 years, Dr. Hirano’s translational research focused on mitochondrial disease and inherited myopathies. His laboratory has identified novel causative genes for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), X-linked scapuloperoneal myopathy, primary coenzyme Q10 (CoQ10) deficiencies and has studied cell and mouse models of these and other diseases including thymidine kinase 2 (TK2) deficiency. He has also been investigating allogeneic hematopoetic stem cell transplantation for MNGIE, pharmacological therapies for TK2 deficiency and, with Kris Engelstad and Dr. Dieter Egli, mitochondrial replacement therapy. Since 2009, Dr. Hirano has directed the NIH U54-funded North American Mitochondrial Disease Consortium (NAMDC).