# Expanded Access Deoxynucleoside Therapy for Thymidine Kinase 2 (TK2) Deficiency

> **NIH NIH U54** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $187,436

## Abstract

Thymidine kinase 2 (TK2) is required for synthesis of pyrimidine deoxynucleoside triphosphate
building blocks for mitochondrial DNA (mtDNA) synthesis. Autosomal recessive TK2 mutations
cause depletion and multiple deletions of mtDNA that manifest predominantly as a myopathy
usually beginning in childhood and progressing relentlessly. Based upon our pre-clinical studies
in a Tk2 H126N knockin mouse model demonstrated efficacy of deoxynucleoside monophosphate
and deoxynucleoside therapies, we have administered these treatments to 30 patients
internationally on an expanded access basis. In a retrospective analysis of 16 genetically
confirmed TK2 deficient patients who had received treatment for at least one year, we observed
stabilization or improvements of clinical functions. In the subgroup of 5 patients with early onset
and severe disease, survival and motor functions improved significantly compared to historical
untreated patients. In the 11 childhood- and adult-onset patients, all clinical measures stabilized
or improved. We observed increases in the 6-minute walk test. Three of 8 patients who were non-
ambulatory at baseline gained ability to walk on therapy; 4 of 5 patients who required enteric
nutrition were able to discontinue feeding tube use; and 2 of 10 patients who required mechanical
ventilation became able to breathe independently. The only side-effect observed in 8 of the 16
patients was dose-dependent diarrhea, which did not require withdrawal of treatment. While our
preliminary data on safety and efficacy of expanded access deoxynucleoside therapy in TK2d
patients are very promising, there are potential concerns about long-term safety and efficacy of
deoxynucleoside therapy that warrant further investigation in this proposed open-label expanded
access multi-center NAMDC study involving three sites.

## Key facts

- **NIH application ID:** 10023970
- **Project number:** 5U54NS078059-10
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** MICHIO HIRANO
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $187,436
- **Award type:** 5
- **Project period:** 2011-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023970

## Citation

> US National Institutes of Health, RePORTER application 10023970, Expanded Access Deoxynucleoside Therapy for Thymidine Kinase 2 (TK2) Deficiency (5U54NS078059-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10023970. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*