Observational studyNeurology2025
Pyrimidine Nucleos(t)ide Therapy in Patients With Thymidine Kinase 2 Deficiency: A Multicenter Retrospective Chart Review Study.
Observational study in Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03701568 (A RETROspective Study of the Combination of Pyrimidine Nucleos), which is not on this map. Cited by 11 papers.
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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.
A RETROspective Study of the Combination of Pyrimidine Nucleos(t)Ides in Patients With Thymidine Kinase 2 Deficiency (TK2)
Who cites it
11 citing papers in PubMed.
- Genetic Diagnosis in Epilepsy: Implications for Clinical Management.Current neurology and neuroscience reports · 2026Review
- Use of nucleoside therapy for mitochondrial DNA depletion/deletion syndrome (MDDS).Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Advances in Primary Mitochondrial Diseases: Diagnosis, Natural History Studies and Clinical Trials.Genes · 2026Review
- Nucleoside therapy for thymidine kinase 2 deficiency: Long-term outcomes from a Brazilian cohort.Journal of neuromuscular diseases · 2026Article
- A year in pharmacology: new drugs approved by the US food and drug administration in 2025.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Non-invasive biomarkers for diagnosis and monitoring of primary mitochondrial diseases.Journal of neurology · 2026Review
- 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
- Disease burden of untreated thymidine kinase 2 deficiency: insights from a large patient dataset.Brain communications · 2026Article
- Efficacy and safety of pyrimidine nucleos(t)ide therapy in thymidine kinase 2 deficiency.Brain communications · 2026Article
- Patients' lived experience of thymidine kinase 2 deficiency: the online survey-based assessment of TK2d patient perspectives study.Therapeutic advances in rare diseaseArticle
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
BACKGROUND AND
objectivesThymidine kinase 2 deficiency (TK2d) is an ultra-rare, progressive, and life-threatening mitochondrial myopathy caused by pathogenic variants of the thymidine kinase 2 gene. Patients often lose the ability to walk, eat, and breathe independently. There are no approved therapies; however, preclinical studies of pyrimidine nucleos(t)ide therapy have shown promising results. We investigated the safety and efficacy of pyrimidine nucleos(t)ide therapy in patients with TK2d.
methodsMedical records of children and adults with TK2d receiving pyrimidine nucleosides or nucleotides (≤800 mg/kg/d deoxycytidine and deoxythymidine [or their monophosphates]) were collected retrospectively from clinical sites globally. Data included baseline characteristics, medical history, disease-related outcomes, and treatment safety. To assess survival benefit, treated patients were compared with untreated TK2d controls from the literature.
resultsBaseline demographics and clinical characteristics were comparable between treated (n = 38) and untreated (n = 69) patients. Among treated patients (55.3% male; 44.7% female), the median age of TK2d symptom onset was 2.46 years. None of the treated patients (0/38) and 58% (40/69) of untreated patients died. For time to death from TK2d symptom onset or treatment start, treated patients had a reduced risk of death compared with untreated patients (85%-93% [hazard ratio 0.067-0.147] vs 75%-91% [0.091-0.251], respectively). Exact conditional logistic regression analyses confirmed a 95% reduction in risk of death (odds ratios 0.044-0.047; all DISCUSSION: These results indicate that pyrimidine nucleos(t)ide therapy was generally well tolerated; had an acceptable safety profile; and may reduce risk of death, positively change disease trajectory, and stabilize or improve symptoms in patients with TK2d. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT03701568. First submitted: September 27, 2018; first participant consented: October 30, 2018. clinicaltrials.gov/study/NCT03701568. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence for a reduction in the risk of death in patients with TK2d treated with pyrimidine nucleos(t)ides.
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