ReviewJournal of neuromuscular diseases2022
Advances in Thymidine Kinase 2 Deficiency: Clinical Aspects, Translational Progress, and Emerging Therapies.
Review in Journal of neuromuscular diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06754098 (An Off-Label Single Arm Clinical Study to Evaluate the Efficacy and Safety of Doxecitin and Doxribthymine in Adult Subjects With Thymidine Kinase 2), which is not on this map. Cited by 25 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.
An Off-Label Single Arm Clinical Study to Evaluate the Efficacy and Safety of Doxecitin and Doxribthymine in Adult Subjects With Thymidine Kinase 2 (TK2) Deficiency.
Who cites it
25 citing papers in PubMed, 26 citations in OpenAlex.
- Assessing a Mitochondrial Disease Treatment via a Novel Statistical Technique for Accelerometer Data.Annals of clinical and translational neurology · 2025Trial
- Use of nucleoside therapy for mitochondrial DNA depletion/deletion syndrome (MDDS).Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Nucleoside therapy for thymidine kinase 2 deficiency: Long-term outcomes from a Brazilian cohort.Journal of neuromuscular diseases · 2026Article
- 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
- Mitochondrial Transplantation as a Therapeutic Strategy for Inherited Mitochondrial Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Efficacy and safety of pyrimidine nucleos(t)ide therapy in thymidine kinase 2 deficiency.Brain communications · 2026Article
- Exploring Outcome Measures for Mitochondrial Myopathies; Insights From a Longitudinal Study on TK2 Deficiency.Journal of inherited metabolic disease · 2026Article
- Disease burden of untreated thymidine kinase 2 deficiency: insights from a large patient dataset.Brain communications · 2026Article
- Mitochondrial Dysfunction in Cardiomyopathy and Heart Failure: From Energetic Collapse to Therapeutic Opportunity.Biomolecules · 2025Review
- Pyrimidine Nucleos(t)ide Therapy in Patients With Thymidine Kinase 2 Deficiency: A Multicenter Retrospective Chart Review Study.Neurology · 2025Observational
- National diagnostic gaps for TK2 Deficiency in Italy: insights from the AIM Multicenter Survey.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2025Article
- RRM2B deficiency causes dATP and dGTP depletion through enhanced degradation and slower synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Novel biallelic TK2 mutations cause mitochondrial DNA depletion syndrome with infantile early-onset lipid storage myopathy.Orphanet journal of rare diseases · 2025Article
- Clinical and molecular spectrum of TK2-deficiency: a large Brazilian cohort.Scientific reports · 2025Article
- Mitochondrial DNA depletion syndrome and its cardiac complication.Frontiers in cardiovascular medicine · 2025Review
- Roles of nucleotide metabolism in pancreatic cancer.Frontiers in immunology · 2025Review
- Guanylate Kinase 1 Deficiency: A Novel and Potentially Treatable Mitochondrial DNA Depletion/Deletions Disease.Annals of neurology · 2024Article
- The senescence-associated secretome of Hedgehog-deficient hepatocytes drives MASLD progression.The Journal of clinical investigation · 2024Article
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- Mitochondrial Chronic Progressive External Ophthalmoplegia.Brain sciences · 2024Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Defects in the replication, maintenance, and repair of mitochondrial DNA (mtDNA) constitute a growing and genetically heterogeneous group of mitochondrial disorders. Multiple genes participate in these processes, including thymidine kinase 2 (TK2) encoding the mitochondrial matrix protein TK2, a critical component of the mitochondrial nucleotide salvage pathway. TK2 deficiency (TK2d) causes mtDNA depletion, multiple deletions, or both, which manifest predominantly as mitochondrial myopathy. A wide clinical spectrum phenotype includes a severe, rapidly progressive, early onset form (median survival: < 2 years); a less severe childhood-onset form; and a late-onset form with a variably slower rate of progression. Clinical presentation typically includes progressive weakness of limb, neck, facial, oropharyngeal, and respiratory muscle, whereas limb myopathy with ptosis, ophthalmoparesis, and respiratory involvement is more common in the late-onset form. Deoxynucleoside monophosphates and deoxynucleosides that can bypass the TK2 enzyme defect have been assessed in a mouse model, as well as under open-label compassionate use (expanded access) in TK2d patients, indicating clinical efficacy with a favorable side-effect profile. This treatment is currently undergoing testing in clinical trials intended to support approval in the US and European Union (EU). In the early expanded access program, growth differentiation factor 15 (GDF-15) appears to be a useful biomarker that correlates with therapeutic response. With the advent of a specific treatment and given the high morbidity and mortality associated with TK2d, clinicians need to know how to recognize and diagnose this disorder. Here, we summarize translational research about this rare condition emphasizing clinical aspects.
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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.