Treatment of TK2 Deficiency With Thymidine and Deoxycytidine
| Status: | Enrolling by invitation |
|---|---|
| Healthy: | No |
| Age Range: | Any |
| Updated: | 8/25/2018 |
| Start Date: | May 16, 2017 |
| End Date: | April 1, 2024 |
Deoxythymidine and Deoxycytidine Treatment for Thymidine Kinase 2 (TK2) Deficiency
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.
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.
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.
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.
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
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