HOW DO DEOXYNUCLEOSIDE REPLACEMENT THERAPIES WORK?
Deoxynucleoside replacement therapies are a specialized class of treatments developed for progressive and potentially fatal mitochondrial myopathy caused by thymidine kinase 2 (TK2) deficiency, a rare genetic disorder that primarily affects infants and children. TK2 deficiency leads to impaired mitochondrial DNA (mtDNA) replication, resulting in progressive neuromuscular dysfunction. Unlike supportive care, this therapeutic approach targets the underlying metabolic defect rather than only managing symptoms.
These therapies work by supplying exogenous deoxynucleosides, most commonly deoxythymidine and deoxycytidine, to replenish depleted intracellular deoxynucleotide pools. The supplemented nucleosides bypass the defective mitochondrial salvage pathway and are converted into deoxynucleoside triphosphates, which are essential building blocks for mtDNA replication and repair. Restoration of mtDNA synthesis helps improve mitochondrial function and cellular energy production.
Kygevvi (doxecitine and doxribtimine) is a first-in-class deoxynucleoside replacement therapy approved by the U.S. FDA in November 2025. It is currently the only FDA-approved therapy specifically indicated for TK2-related mitochondrial DNA depletion disorders in adult and pediatric patients with symptom onset at 12 years of age or younger.
HOW ARE DEOXYNUCLEOSIDE REPLACEMENT THERAPIES USED?
Deoxynucleoside replacement therapies are administered orally for the treatment of thymidine kinase 2 (TK2) deficiency in adult and pediatric patients with symptom onset at 12 years of age or younger. The therapy is supplied as a powder for oral administration that must be mixed with water and taken three times daily with food.
WHAT ARE SIDE EFFECTS OF DEOXYNUCLEOSIDE REPLACEMENT THERAPIES?
Common side effects of deoxynucleoside replacement therapies include the following:
- Diarrhea
- Abdominal Pain
- Vomiting
- Increased Alanine Aminotransferase (ALT)
- Increased Aspartate Aminotransferase (AST)
Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.
