deoxycytidine and deoxythymidine for Mitochondrial Encephalomyopathies

Phase-Based Estimates
1
Effectiveness
2
Safety
Research InstituMcGill University Health Centre - Children Hospital of Montreal, Montréal, Canada
+7 More
deoxycytidine and deoxythymidine - CombinationProduct
Eligibility
< 65
All Sexes
Eligible conditions
Mitochondrial Encephalomyopathies

Study Summary

This study is evaluating whether a mix of deoxynucleosides can improve symptoms in people with mitochondrial DNA depletion syndromes.

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Eligible Conditions

  • Mitochondrial Encephalomyopathies
  • Mitochondrial Diseases
  • Metabolic Diseases
  • Brain Diseases
  • Mitochondrial Encephalomyopathy
  • Mitochondrial DNA Depletion
  • Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke Like Episodes (MELAS)
  • Mitochondrial Metabolism Disorders

Treatment Effectiveness

Effectiveness Estimate

1 of 3

Study Objectives

This trial is evaluating whether deoxycytidine and deoxythymidine will improve 1 primary outcome and 1 secondary outcome in patients with Mitochondrial Encephalomyopathies. Measurement will happen over the course of 26 weeks.

26 weeks
Number of participants experiencing dose-limiting toxicities, adverse events (AEs), serious adverse events (SAEs)
Rate of Responder versus Non-Responder Status with investigational product

Trial Safety

Safety Estimate

2 of 3
This is better than 68% of similar trials

Trial Design

2 Treatment Groups

Control
dC/dT100-400 Arm

This trial requires 15 total participants across 2 different treatment groups

This trial involves 2 different treatments. Deoxycytidine And Deoxythymidine is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 2 and have already been tested with other people.

dC/dT100-400 Arm
CombinationProduct
Children 0-18 Y who takes the investigational product deoxynucleosides pyrimidine (mix of deoxycytidine and deoxythymidine), following the protocol.
ControlNo treatment in the control group

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: 26 weeks
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly 26 weeks for reporting.

Who is running the study

Principal Investigator
K. M.
Kenneth Myers, MD
McGill University Health Centre/Research Institute of the McGill University Health Centre

Closest Location

Research InstituMcGill University Health Centre - Children Hospital of Montreal - Montréal, Canada

Eligibility Criteria

This trial is for patients born any sex aged 65 and younger. There are 5 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
Children 0 -18 Y
Written informed consent obtained
You have a clinical diagnosis of a mitochondrial depletion disorder. show original
Pathogenic variant(s) in one of the following genes: POLG, C10orf2, RRM2B, MPV17, SUCLA2, SUCLG1, FBXL4
Negative urinary pregnancy test at screening Agree to use effective contraception for the duration of the study

Patient Q&A Section

Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

Can mitochondrial encephalomyopathies be cured?

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Current treatment has largely stabilized the disease course and improved disability scores. Although there is no cure for these mitochondrial disorders, it is important for patients to receive treatment when possible.

Unverified Answer

What is mitochondrial encephalomyopathies?

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Different diseases fall into this category of mitochondrial encephalomyopathies. Mitochondrial encephalopathy is commonly associated to lactic breath, eye movement, or other neurological abnormalities. Mitochondrial encephalomyopathies can be further classified into a number of different disease syndromes. Mitochondrial diseases are generally inherited recessive.

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How many people get mitochondrial encephalomyopathies a year in the United States?

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Based on these data, in the United States approximately 2/100,000 people a year are newly diagnosed with MELAS, and MELA. One of the goals in the MELAS Foundation is to make an MELAS clinical diagnosis readily available to U.S. teenagers without compromising their access to other medical care.

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What are the signs of mitochondrial encephalomyopathies?

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Mitochondrial encephalomyopathies can present with symptoms including cognitive and behavioral changes, headaches, blurred vision, vomiting, or muscle weakness. An abnormal signal on electroencephalography or a rise in the level of creatine kinase in serum or urine may indicate mitochondrial encephalomyopathy.\n

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What causes mitochondrial encephalomyopathies?

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This review suggests that there are a variety of causes for multiple encephalomyopathies; a possible common root cause involves mitochondrial dysfunction, and this review suggests that a unifying cause must be sought for all encephalomyopathies.

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What are common treatments for mitochondrial encephalomyopathies?

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There are a number of treatments discussed in MEO, but only a few are commonly used, particularly in the context of MEO, such as high-protein, low-carbohydrate diets, and the use of high-dose oral glucose. There is an urgent need for new treatment options. For some of the treatment details discussed herein, more recent research evidence is currently lacking, whereas the others are well established.

Unverified Answer

What is the latest research for mitochondrial encephalomyopathies?

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Mitochondrial DNA mutations are the main cause of mitochondrial encephalomyopathies, but nuclear mutations are found in about 30% of patients with multiple system atrophy and leukoencephalopathy. The clinical presentation of mitochondrial encephalomyopathies varies widely, but the disease has an insidious clinical course. The treatment of mitochondrial and nuclear encephalomyopathies remains inadequate. The clinical course of multiple system atrophy is variable. There is no known cure for mitochondrial or nuclear encephalomyopathies.

Unverified Answer

What are the latest developments in deoxycytidine and deoxythymidine for therapeutic use?

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New insights into the mechanisms of action of DCTP and DTT will help clarify the role of these agents in the treatment and the prognosis of myelodysplastic syndromes and other disorders characterized by defective nuclear energy production. The development of new chemotherapy agents, such as the inhibitors of thymidylate biosynthesis, which represent a new treatment approach for cancers and leukemia, is still under investigation.

Unverified Answer

Have there been any new discoveries for treating mitochondrial encephalomyopathies?

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We have identified only 9 new therapies. Most of these therapies are under development and await clinical assessment. They may be in use in the future.

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How does deoxycytidine and deoxythymidine work?

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Cytidine and thymidine are chemically similar in that they both contain a pyrimidine base (carbons 7 and 8 in the diagram) and have the same hydrogen atoms of the two rings adjacent to one another (at the carbons 1 and 5). The cytotoxic properties of nucleosides involve blocking the enzymatic activity of DNA polymerase. Deoxycytidine and deoxythymidine work by deactivating DNA polymerase to prevent DNA replication. Deoxycytidine interacts with the pyridine subunit, and deoxythymidine blocks deoxycytidine interaction on pyridine subunit. In contrast, in thymidine, the 2-carbon group replaces the methyl group.

Unverified Answer

What is the average age someone gets mitochondrial encephalomyopathies?

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The average age of onset for the mitochondrial encephalomyopathies is in early childhood and early adulthood, with a relatively stable age of onset over a lifetime. This suggests that, the mitochondrial disorder is a spectrum of disorders and there may be an age of onset that is different across different disorders.

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What are the common side effects of deoxycytidine and deoxythymidine?

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These two nucleoside analogues have very similar toxicities. Among their common toxicities, oral administration of deoxycytidine may cause nausea and vomiting, diarrhoea, abdominal pain, and leukopenia. Deoxythymidine should be used with caution, and the infusion rate should be decreased in patients receiving this treatment.

Unverified Answer
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