Deoxycytidine + Deoxythymidine for Telomere Biology Disorder

Overseen By Elizabeth Korn, BS

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Suneet Agarwal

Must not be taking: Androgens, Growth factors

Disqualifiers: Severe aplastic anemia, Chronic diarrhea, Kidney disease, High-risk myelodysplastic syndrome, others

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

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new combination of two medications, deoxycytidine (dC) and deoxythymidine (dT), is safe for people with telomere biology disorders. These disorders can cause bone marrow problems, lung issues, and blood abnormalities. The trial aims to determine if these medications can improve these conditions over six months. Potential participants should have a known telomere biology disorder and related symptoms, such as blood or lung issues. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications intended to improve blood cell production, like androgens or growth factors, at least 30 days before joining. Other medications that could interfere with the study may also need to be stopped, as determined by the study doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that combining deoxycytidine (dC) and deoxythymidine (dT) has been tested for safety in children with certain genetic disorders. Early results suggest this combination is generally safe and tolerable for both children and adults with telomere biology disorders, which affect the protective ends of chromosomes. Although extensive safety data in humans is limited, studies indicate that the treatment does not cause severe side effects. As this is an early-stage trial, researchers continue to closely monitor the treatment's safety. While the treatment appears promising, it remains important to watch for any negative effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using Deoxycytidine and Deoxythymidine for treating Telomere Biology Disorder because these compounds target the root cause of the condition by focusing on telomere maintenance. Unlike existing treatments that might only address symptoms, these nucleosides aim to directly impact the genetic stability and cellular aging process. By potentially enhancing telomere function, they offer a novel approach that could improve cell health and longevity, making them a promising option for patients with this rare disorder.

What evidence suggests that this treatment might be an effective treatment for telomere biology disorders?

Research has shown that combining deoxycytidine (dC) and deoxythymidine (dT) might help treat telomere biology disorders. These disorders relate to issues with the POLG gene, which is crucial for maintaining DNA health. In some studies, patients experienced improvements after taking these drugs for six months. In this trial, participants will take the dC/dT combination therapy three times daily over 24 weeks with dose escalation. The treatment may work by lengthening telomeres, which act as protective caps at the ends of DNA strands. Longer telomeres might alleviate issues related to bone marrow, blood, or lungs in these disorders. ^{1 2 3 4 5}

Who Is on the Research Team?

Helen Reed, MD, MPH

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

This trial is for patients with telomere biology disorders, specifically those who have low blood counts (cytopenias). Participants must be able to take oral medication three times daily, visit Boston Children's Hospital twice, go for additional blood draws six times, and maintain communication with a research nurse.

Inclusion Criteria

I can consume liquids by mouth or through a feeding tube.

Participants must exhibit at least one clinical manifestation associated with a telomere biology disorder, in the judgment of the PI

I am older than 1 year and 60 years old or younger.

Exclusion Criteria

I do not have high-risk blood disorders or any other active cancer.

Participants must not be on other medications or study agents or have other uncontrolled intercurrent illness that could interfere with study interpretation, in the opinion of the study Principal Investigator (PI)

Participants must not have psychological or social conditions that would limit adherence with study requirements, in the opinion of the study PI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enteral nucleoside therapy with dose escalation for 24 weeks

24 weeks

2 visits (in-person), 6 lab visits, 9 phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 phone call

What Are the Treatments Tested in This Trial?

Interventions

• Deoxycytidine
• Deoxythymidine

Trial Overview The trial is testing the safety of a combination therapy using deoxycytidine (dC) and deoxythymidine (dT) in patients with telomere biology disorders. It aims to see if this treatment can improve blood counts over a period of 24 weeks with regular monitoring.

How Is the Trial Designed?

Group I: dC/dT Experimental Treatment 2 Interventions

Participants will take study therapy three times daily over 24 weeks with dose escalation.

Who Is Running the Clinical Trial?

Suneet Agarwal

Lead Sponsor

Trials

1

Recruited

40+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06817590

Nucleoside Therapy in Patients With Telomere Biology ... The goal of this clinical trial is to learn if a combination therapy of deoxycytidine (dC) plus deoxythymidine (dT) is safe in patients with telomere ...

2. withpower.com withpower.com/trial/phase-1-telomere-biology-disorders-5-2025-478fd

Deoxycytidine + Deoxythymidine for Telomere Biology ... The goal of this clinical trial is to learn if a combination therapy of deoxycytidine (dC) plus deoxythymidine (dT) is safe in patients with telomere ...

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

Safety and efficacy of deoxycytidine/deoxythymidine ... We assessed the safety and efficacy of combination therapy with deoxycytidine and deoxythymidine (dC/dT) in children with POLG-related disorders.

4. answers.childrenshospital.org answers.childrenshospital.org/new-research-telomeres/

New research paves the way to a better understanding of ... After introducing eTERC into different types of cells, the team found that just one exposure appeared to increase telomere length in human stem ...

5. researchgate.net researchgate.net/publication/382786301_Safety_and_efficacy_of_deoxycytidinedeoxythymidine_combination_therapy_in_POLG-related_disorders_6-month_interim_results_of_an_open-label_single_arm_phase_2_trial

6-month interim results of an open-label, single arm, phase ... Deoxycytidine and deoxythymidine (dC/dT) has been regarded as a treatment option for patients with POLG-related disorders with the evidence of ...