Use of nucleoside therapy for mitochondrial DNA depletion/deletion syndrome (MDDS)

On November 3, 2025, the U.S. Food and Drug Administration (FDA) approved deoxycytidine/deoxythymidine (dC/dT) pyrimidine nucleoside therapy for clinical use in thymidine kinase 2 deficiency (TK2d), an ultra-rare autosomal recessive mitochondrial disease affecting patients with symptomatic onset at or before 12 years of age [1]. The European Commission subsequently granted marketing authorization on March 26, 2026 [2]. These approvals were based upon evidence from a pivotal phase 2 clinical trial, two retrospective multicenter chart reviews, and an expanded access program [3,4].