Results published in Neurology have highlighted a 95% reduction in the risk of death among patients treated with pyrimidine nucleoside and/or nucleotide therapy for thymidine kinase 2 deficiency (TK2d), a rare mitochondrial disorder.
The findings, from a multicentre retrospective chart review, represent the first published data exploring the safety and efficacy of this investigational therapy in TK2d. The analysis showed that none of the 38 treated patients died, compared with 58% mortality in the untreated group (40 out of 69). Overall, treatment was associated with a 95% lower risk of death and improved motor function and respiratory support outcomes.
TK2d is an ultra-rare, life-threatening, genetic mitochondrial disease that causes progressive muscle weakness, affecting movement, swallowing, and breathing. Currently, there are no approved therapies or international treatment guidelines.
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In treated patients, 65% who had previously lost motor milestones regained at least one milestone after starting therapy, while 29% experienced a reduction in their need for ventilatory support. Most treatment-emergent adverse events were mild, with diarrhoea, elevated creatine kinase, and mild increases in liver enzymes among the most frequently reported.
Study authors noted some limitations, including small sample size and data variability across centres. However, they emphasised the strong survival benefit observed, underscoring the potential clinical impact of pyrimidine nucleoside and/or nucleotide therapy.
UCB’s pyrimidine nucleoside therapy is currently under regulatory review in the US and EU. If approved, it will be the first and only treatment available for patients with TK2d whose symptoms began before the age of 12.
This publication underscores the significance of these data for the TK2d community. These findings highlight the potential of pyrimidine nucleoside and/or nucleotide therapy as a clinically important therapeutic option.
Cristina Domínguez-González, lead author of the study
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This news item has been summarised using AI and checked by humans before publication.
Sources
Neurology; UCB press release, 13 October 2025
Domínguez-González C, et al. Pyrimidine Nucleos(t)ide Therapy in Patients With Thymidine Kinase 2 Deficiency. Neurology. 2025;105(6):e213908.
→ This is the main publication the news item is based on, containing the study data reported by UCB.
Thymidine kinase 2 deficiency. National Organization for Rare Disorders. Updated April 3, 2025.
→ Provides authoritative background information on TK2d as a rare mitochondrial disorder.
Garone C, et al. Retrospective natural history of thymidine kinase 2 deficiency. J Med Genet. 2018;55(8):515-21.
→ Supports the background discussion of disease progression and prognosis in untreated TK2d patients, relevant to comparison with treated cohorts.
About thymidine kinase 2 deficiency (TK2d)
Mitochondrial diseases, like TK2d, affect energy-demanding parts of the body such as muscles, heart, and brain.4,5,8 TK2d is generally categorized as: age of symptom onset ≤12 years and >12 years.3,4,5 TK2d presents with varying severity depending on the age of onset, with cases in the population with age of symptom onset ≤12 years typically being the most rapidly progressing and cases in the population with age of symptom onset >12 years slower progressing.3,4,5 The estimated worldwide prevalence of TK2d is 1.64 [0.5, 3.1] cases per 1,000,000 people.9
TK2d profoundly affects multiple health, physical, quality-of-life, and psychosocial domains, as children struggle to achieve developmental milestones or lose them, and adults lose functional independence with challenges in breathing, eating, and walking.10,11
About doxecitine and doxribtimine
Administration of doxecitine and doxribtimine is intended to incorporate the pyrimidine nucleosides, deoxycytidine and deoxythymidine, into skeletal muscle mitochondrial deoxyribonucleic acid (DNA). This action restores mitochondrial DNA copy number in TK2d mutant mice, as suggested by preclinical data.12,13,14
The safety and efficacy of doxecitine and doxribtimine combination therapy has not been established and is not currently approved for use by any regulatory authority worldwide. It is currently under regulatory review by US and EU regulatory authorities.
