NCT03639701

Treatment of TK2 Deficiency With Thymidine and Deoxycytidine

Deoxythymidine and Deoxycytidine Treatment for Thymidine Kinase 2 (TK2) Deficiency

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Columbia University · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Mitochondrial DNA Depletion Syndrome 2 Myopathic Type
• Thymidine Kinase 2 Deficiency

Interventions

Type	Name	Description
DRUG	Thymidine	Mitochondrial DNA nucleotide precursors. Dose escalation: 130mg/kg/day x 14 days, 260 mg/kg/day x 14 days, and 400mg/kg/day as tolerated. Compounds are taken orally and divided into 3 doses daily.

Timeline

• Start date: 2017-05-16
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2018-08-21
• Last updated: 2026-01-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study