Treatment of TK2 Deficiency With Thymidine and Deoxycytidine

• Status: Enrolling by invitation
• Trial end date: 2024-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Patients with confirmed mitochondrial DNA depletion syndrome 2 (thymidine kinase 2 [TK2] deficiency) have reduced levels of nucleotides (deoxythymidine monophosphate and deoxycytidine monophosphate) for mitochondrial DNA synthesis. This results in mitochondrial DNA depletion syndrome (i.e less number of functional mitochondrial DNA). Patients with confirmed TK2 deficiency will be treated with open label deoxythymidine (dThd) and deoxycytidine (dCyt), which are nucleotide precursors, with the expectation that the cells could make additional mitochondrial DNA. This in turn may help reduce the clinical symptoms.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Columbia University
• Collaborators: Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), Spain; Hospital Universitario 12 de Octubre; Hospitales Universitarios Virgen del Rocío; Instituto de Salud Carlos III; Medical Research Council Mitochondrial Biology Unit; Muscular Dystrophy Association; University of Seville; Vall d'Hebron Research Institute

Criteria

Inclusion Criteria:

• Genetically confirmed diagnosis of TK2 deficiency

• Deemed by principle investigator to be symptomatic with TK2 deficiency

• Single gene disease; absence of polygenic disease

• Hematocrit within normal range for age group

• Patient or patient's guardian able to consent and comply with protocol requirements

• Presence of caregiver to ensure study compliance (if needed)

• Abstention from use of all pill-form dietary supplements and non-prescribed medications (except as allowed by the investigator)

• Abstention from use of other investigational medications or other medications according to the study investigator

Exclusion Criteria:

• Clinical history of bleeding or abnormal prothrombin time (PT)/partial thromboplastin time (PTT)

• Hepatic insufficiency with liver function tests (LFTs) greater than two times normal

• Renal insufficiency requiring dialysis

• Any other concurrent inborn errors of metabolism

• Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in lactic acidosis