ArticleAnnals of neurology2017
Deoxycytidine and Deoxythymidine Treatment for Thymidine Kinase 2 Deficiency.
Article in Annals of neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03639701 (Deoxythymidine and Deoxycytidine Treatment for Thymidine Kinase 2), which is not on this map. Cited by 58 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Deoxythymidine and Deoxycytidine Treatment for Thymidine Kinase 2 (TK2) Deficiency
Who cites it
58 citing papers in PubMed, 115 citations in OpenAlex.
- Investigating the safety and efficacy of deoxycytidine/deoxythymidine in mitochondrial DNA depletion disorders: phase 2 open-label trial.Journal of neurology · 2025Trial
- Mitochondrial NADP(H)-dependent de novo dTMP biosynthesis counteracts the cytotoxicity of PARP inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Genetic Diagnosis in Epilepsy: Implications for Clinical Management.Current neurology and neuroscience reports · 2026Review
- Preclinical and first-in-human evidence of 4-hydroxybenzoic acid for mitochondrial COQ2 deficiency.Brain : a journal of neurology · 2026Article
- Short telomeres in mitochondrial DNA depletion disorders.Mitochondrion · 2026Article
- Doxecitine and Doxribtimine: First Approval.Paediatric drugs · 2026Review
- Effect of Renal Impairment on the Pharmacokinetics and Safety of Doxecitine and Doxribtimine: A Single-Dose Phase 1 Study.Clinical pharmacology in drug development · 2026Article
- Efficacy and safety of pyrimidine nucleos(t)ide therapy in thymidine kinase 2 deficiency.Brain communications · 2026Article
- Gene therapy and mRNA drugs approach for mitochondrial OXPHOS deficiencies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Pyrimidine Nucleos(t)ide Therapy in Patients With Thymidine Kinase 2 Deficiency: A Multicenter Retrospective Chart Review Study.Neurology · 2025Observational
- Therapies for Mitochondrial Disease: Past, Present, and Future.Journal of inherited metabolic disease · 2025Review
- Deoxynucleoside supplementation ameliorates the disease associated phenotypes in a zebrafish model of RRM2B mtDNA depletion syndrome.Human molecular genetics · 2025Article
- Infantile TK2 Deficiency Causing Mitochondrial Encephalomyopathy With Migrating Focal Seizures.Neurology · 2025Article
- Novel biallelic TK2 mutations cause mitochondrial DNA depletion syndrome with infantile early-onset lipid storage myopathy.Orphanet journal of rare diseases · 2025Article
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Guanylate Kinase 1 Deficiency: A Novel and Potentially Treatable Mitochondrial DNA Depletion/Deletions Disease.Annals of neurology · 2024Article
- Safety and efficacy of deoxycytidine/deoxythymidine combination therapy in POLG-related disorders: 6-month interim results of an open-label, single arm, phase 2 trial.EClinicalMedicine · 2024Article
- Clinical Approaches for Mitochondrial Diseases.Cells · 2023Review
- Nucleoside Analogs: A Review of Its Source and Separation Processes.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 4 countries.
Funding
Abstract
objectiveThymidine kinase 2 (TK2), a critical enzyme in the mitochondrial pyrimidine salvage pathway, is essential for mitochondrial DNA (mtDNA) maintenance. Mutations in the nuclear gene, TK2, cause TK2 deficiency, which manifests predominantly in children as myopathy with mtDNA depletion. Molecular bypass therapy with the TK2 products, deoxycytidine monophosphate (dCMP) and deoxythymidine monophosphate (dTMP), prolongs the life span of Tk2-deficient (Tk2
methodsTo test these hypotheses, we assessed two therapies in Tk2
resultsWe observed that dC+dT delayed disease onset, prolonged life span of Tk2-deficient mice and restored mtDNA copy number as well as respiratory chain enzyme activities and levels. In contrast, dCMP+dTMP+THU therapy decreased life span of Tk2
interpretationOur studies demonstrate that deoxynucleoside substrate enhancement is a novel therapy, which may ameliorate TK2 deficiency in patients. Ann Neurol 2017;81:641-652.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.