Treatment of TK2 Deficiency with Thymidine and Deoxycytidine

Columbia University

Status and phase

Active, not recruiting

Phase 2

Phase 1

Conditions

Thymidine Kinase 2 Deficiency

Mitochondrial DNA Depletion Syndrome 2 Myopathic Type

Treatments

Drug: Thymidine

Study type

Interventional

Funder types

Other

Identifiers

NCT03639701

AAAQ7552

Details and patient eligibility

About

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.

Full description

Mitochondrial are responsible for the production of cellular energy. Mitochondria contain DNA which is the encoding system ( "recipe") for making the proteins that allow the mitochondria to function. Reduced amount of mitochondrial DNA, caused by genetic mutations in certain genes, Mitochondrial DNA Depletion Syndrome. This can result in symptoms; such as fatigue, weakness, and deficiencies in various body systems. TK2 deficiency is considered a mitochondrial depletion syndrome. Patients with TK2 deficiency have weakness and walking difficulty. They also have depleted levels of chemicals (phosphorylated deoxythymidine and deoxycytidine) used to make mitochondrial DNA. Based on previous studies with a similar compound, patients reported more energy and better motor skills.

Eligible patients include those with genetic mutations in the TK2 gene who are willing to attend several outpatient visits, and have motor skills testing, neurological exam by doctor, and blood samples.

Enrollment

23 patients

Sex

All

Volunteers

No Healthy Volunteers

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