Nucleotide Precursors for TK2 Deficiency

Not currently recruiting at 2 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Columbia University

Must not be taking: Dietary supplements

Disqualifiers: Bleeding history, Hepatic insufficiency, Renal insufficiency, Inborn errors, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Up to 60 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with TK2 deficiency, a condition that disrupts energy production in cells. The treatment administers two substances, deoxythymidine (dThd) and deoxycytidine (dCyt), which may boost mitochondrial DNA production and alleviate symptoms. The trial is open to those with a confirmed genetic diagnosis of TK2 deficiency who are symptomatic. Participants must have a caregiver to assist with study requirements and adhere to specific guidelines regarding medications and supplements. As a Phase 1, Phase 2 trial, this research aims to understand the treatment's effects and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking medical advancements.

Will I have to stop taking my current medications?

The trial requires participants to stop using all pill-form dietary supplements and non-prescribed medications, unless allowed by the investigator. You also need to avoid other investigational medications or other medications as per the study investigator's guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments deoxythymidine (dThd) and deoxycytidine (dCyt) are generally well-tolerated by patients. These treatments significantly reduce the risk of death in patients with thymidine kinase 2 (TK2) deficiency, a rare genetic disorder affecting the energy-producing parts of cells. Importantly, past trials revealed no serious side effects, suggesting these treatments are safe. However, like any treatment, side effects may occur. Participants should discuss potential risks with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments deoxycytidine (dCyt) and deoxythymidine (dThd) for TK2 deficiency because they offer a unique approach compared to existing therapies. Unlike current options, which mainly focus on supportive care and managing symptoms, these treatments directly supply the nucleotide precursors that are lacking in patients with TK2 deficiency. This innovative strategy aims to address the root cause of the mitochondrial dysfunction seen in this rare genetic condition, providing hope for more effective management and improved quality of life for affected individuals.

What evidence suggests that this treatment might be an effective treatment for TK2 deficiency?

Research has shown that certain treatments can greatly help people with TK2 deficiency. In this trial, all participants will receive an open-label combination of thymidine and deoxycytidine. These treatments have reduced the risk of death by 95% for these patients. Recipients of this therapy report increased energy and improved movement skills. This suggests that the treatment may help produce more mitochondrial DNA, essential for cell function. Overall, these findings indicate a promising option for managing TK2 deficiency. ^{2 3 6 7 8}

Who Is on the Research Team?

Michio Hirano, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for patients with genetically confirmed TK2 deficiency, a condition affecting mitochondrial DNA. Participants must not be taking other investigational drugs or certain supplements and should have normal blood counts. They need to consent to the study rules and may require a caregiver's help to follow the protocol.

Inclusion Criteria

Presence of caregiver to ensure study compliance (if needed)

Abstention from use of other investigational medications or other medications according to the study investigator

I do not take any pill-form dietary supplements or non-prescribed medications.

Exclusion Criteria

I require dialysis for kidney failure.

My liver tests are more than twice the normal levels.

I have a history of bleeding or abnormal blood clotting times.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive open label deoxythymidine and deoxycytidine to address TK2 deficiency

Up to 60 months

Several outpatient visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Deoxycytidine (dCyt)
• Deoxythymidine (dThd)

Trial Overview The trial tests whether giving patients with TK2 deficiency two substances, deoxythymidine (dThd) and deoxycytidine (dCyt), can increase their mitochondrial DNA levels and improve symptoms. It's an open-label study, meaning everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: Open label thymidine and deoxycytidine Experimental Treatment 1 Intervention

All patients will receive open label thymidine and deoxycytidine

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Muscular Dystrophy Association

Collaborator

Trials

38

Recruited

60,800+

Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), Spain

Collaborator

Trials

1

Recruited

20+

Instituto de Salud Carlos III

Collaborator

Trials

320

Recruited

648,000+

Medical Research Council Mitochondrial Biology Unit

Collaborator

Trials

2

Recruited

40+

Hospitales Universitarios Virgen del Rocío

Collaborator

Trials

70

Recruited

20,000+

Universitat Autonoma de Barcelona

Collaborator

Trials

50

Recruited

7,700+

University of Seville

Collaborator

Trials

137

Recruited

37,200+

Hospital Universitario 12 de Octubre

Collaborator

Trials

87

Recruited

49,300+

Published Research Related to This Trial

Supplementation with deoxycytidine and deoxythymidine monophosphates (dCMP+dTMP) in a mouse model of thymidine kinase 2 (TK2) deficiency significantly increased mitochondrial DNA levels and improved mitochondrial function, leading to a prolonged lifespan from 13 days to 34 days with treatment.

This study represents the first effective pharmacological treatment for TK2 deficiency, demonstrating that dCMP/dTMP can effectively bypass the enzyme deficiency and ameliorate biochemical defects associated with the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency. Garone, C., Garcia-Diaz, B., Emmanuele, V., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5926768/

Deoxycytidine and deoxythymidine treatment for thymidine ... Our studies demonstrate that deoxynucleoside substrate enhancement is a novel therapy, which may ameliorate TK2 deficiency in patients.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03639701

Treatment of TK2 Deficiency With Thymidine and ... Based on previous studies with a similar compound, patients reported more energy and better motor skills.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2589537024003195

Safety and efficacy of deoxycytidine/deoxythymidine ... This study presents the first human data regarding the safety and efficacy of dC/dT in a mitochondrial DNA depletion disorder other than TK2 deficiency. Our ...

4. ucb.com ucb.com/newsroom/press-releases/article/results-published-in-neurology-highlight-a-95-reduction-in-risk-of-death-with-pyrimidine-nucleostide-therapy-in-patients-with-thymidine-kinase-2-deficiency-tk2d

Results published in Neurology highlight a 95% reduction ... Results published in Neurology highlight a 95% reduction in risk of death with pyrimidine nucleos(t)ide therapy in patients with thymidine ...

5. ucb-usa.com ucb-usa.com/stories-media/UCB-U-S-News/detail/article/new-data-on-investigational-therapy-for-thymidine-kinase-2-deficiency-presented-at-muscular-dystrophy-association-mda-2025-conference

New data on investigational therapy for thymidine kinase 2 ... Clinical data highlight survival benefits and improvement in functional motor outcomes associated with treatment with doxecitine (dC) and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11293517/

Safety and efficacy of deoxycytidine/deoxythymidine ... This study presents the first human data regarding the safety and efficacy of dC/dT in a mitochondrial DNA depletion disorder other than TK2 ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0149291824001437

Pharmacokinetics and Safety of a 1:1 Mixture of Doxecitine ... Introduction. Thymidine kinase 2 (TK2) deficiency (TK2d) is an ultra-rare mitochondrial DNA (mtDNA) depletion and multiple deletion syndrome.

8. rarediseaseadvisor.com rarediseaseadvisor.com/hcp-resource/thymidine-kinase-2-deficiency-clinical-trials/

Thymidine Kinase 2 Deficiency Clinical Trials The primary outcome measures include the number of participants experiencing adverse events and clinically significant changes from baseline in ...