Grants at a glance - Summer 2018

Michio Hirano, professor of Neurology at Columbia University Irving Medical Center in New York, New York, was awarded an MDA Research Grant totaling $300,000 over 3 years to support an open-label expanded access trial of deoxynucleoside therapy for TK2 deficiency. Mitochondrial diseases compose a group of genetic disorders typically affecting multiple organs and are often fatal. Sadly, few treatments are available for these disorders. A subgroup of mitochondrial diseases is mitochondrial DNA depletion syndrome (MDS). MDS encompasses heterogeneous disorders characterized by decreased levels of mitochondrial DNA (mtDNA) in tissues. MDS is caused by mutations in 21 genes required for maintenance of mtDNA. Thymidine kinase 2 (TK2) deficiency is one of the most frequent forms MDS, with an estimated prevalence of 400 patients in the US. The disease typically affects infants or children and causes muscle weakness (myopathy). The disease course is progressive; more than half of the patients require mechanical ventilation and survival is reduced particularly in infants, who usually die within one year of onset. Dr. Hirano and colleagues initially demonstrated that deoxynucleoside treatment dramatically extended the lifespan of their Tk2 mouse model of the human disease. They then obtained approval for compassionate use of deoxynucleosides in TK2-deficient patients. Fifteen patients who have received the therapy have shown clinical improvement by diverse measurements across multiple countries. This study will collect uniform prospective clinical information on the safety and efficacy of this treatment in TK2-deficient patients. The results of this study will inform design of the pivotal clinical trial necessary to obtain FDA approval of the therapy.