Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?

(MitoASD Trial)

Overseen By Michael J Goldenthal, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Drexel University

Must not be taking: Anti-seizure medications

Disqualifiers: Ketogenic diet, Severe cognitive dysfunction, others

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

Compensation: Varies

Number of Visits: 9

Duration: 3 months

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial involves giving children with autism and mitochondrial problems a special mix of vitamins and nutrients called the Mitochondrial Cocktail. The goal is to see if this treatment helps improve their condition by boosting cell energy production and protecting against damage. Researchers will check the children's progress through various tests at different stages of the treatment. The Mitochondrial Cocktail includes cofactors like L-Carnitine and the ketogenic diet, which have shown evidence for use in children with ASD.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants on specialized diets or those needing anti-seizure medications. It's best to discuss your specific medications with the trial investigator.

What data supports the effectiveness of the treatment Mitochondrial Cocktail?

Research shows that enhancing mitochondrial function can improve cancer treatment outcomes. For example, introducing healthy mitochondria into cancer cells has been shown to reduce tumor growth and improve sensitivity to chemotherapy in breast cancer models. ^{1 2 3 4 5}

Is the Mitochondrial Cocktail treatment generally safe for humans?

Some drugs can harm mitochondria, leading to side effects like muscle problems, liver issues, and other health concerns. It's important to know that not all drugs affect mitochondria, but those that do can cause serious health problems. Always consult with a healthcare provider to understand the safety of any treatment. ^{6 7 8 9 10}

How does the Mitochondrial Cocktail treatment differ from other treatments for mitochondrial dysfunction?

The Mitochondrial Cocktail treatment is unique because it focuses on enhancing mitochondrial fusion, which can restore metabolic function in cells with damaged mitochondrial DNA by allowing healthy mitochondria to complement the defective ones. This approach is different from other treatments that may not specifically target the dynamic processes of mitochondrial fusion and fission to improve cellular energy production. ^{11 12 13 14 15}

Research Team

Michael J Goldenthal, PhD

Principal Investigator

Drexel University College of Medicine

Eligibility Criteria

Inclusion Criteria

Subject/legal representative is considered reliable and capable of adhering to the protocol (e.g., able to understand and complete diaries), visit schedule, and medication intake according to the judgment of the investigator.

Subject has a formal diagnosis of autistic spectrum disorders (ASD). the ASD diagnosis will satisfy the DSM- V criteria for ASD, and will be broad-spectrum including both severe and milder cases.

All subjects will have either suspected mitochondrial dysfunction as assessed by clinical evaluation, mitochondrial dysfunction as defined by the presence of significant abnormalities in their buccal mitochondrial respiratory complex activities (i.e., with either respiratory complex I or complex IV deficiencies) or have significantly aberrant specific activity ratios. Subjects with significant deficiencies in either muscle or skin fibroblast respiratory activities will also be included in those cases if buccal mitochondrial respiratory enzyme activity testing has not been performed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the Mitochondrial Cocktail treatment at home once a day for 3 months

3 months

Evaluations at baseline and after 3 months

Non-treatment Observation

Participants are monitored without treatment for an additional 3 months

3 months

Evaluations at 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Mitochondrial Cocktail

Participant Groups

Group I: Mitochondrial Cocktail Experimental Treatment 1 Intervention

The precise content of the Mitochondrial Cocktail will be: * ubiquinol (liquid form, 150 mg/kg subject weight/day * carnitine, 50 mg/kg subject weight/day * alpha-lipoic acid, 100 mg/ day

Who Is Running the Clinical Trial?

Drexel University

Lead Sponsor

Trials

160

Recruited

48,600+

Findings from Research

A study of 27,140 reported cases of rhabdomyolysis identified 14 drugs, including fenofibrate and risperidone, that are linked to mitochondrial toxicity, suggesting a common mechanism for drug-induced muscle damage.

Using murine L6 cells and human skeletal muscle-derived cells, researchers confirmed that these drugs cause significant mitochondrial dysfunction, indicating that the L6 model could be a useful and cost-effective tool for screening potential myotoxic drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing In Vitro Models to Define the Role of Direct Mitochondrial Toxicity in Frequently Reported Drug-Induced Rhabdomyolysis. Bin Dayel, FF., Alfirevic, A., Chadwick, AE.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

Regulation of mitochondrial fusion and mitophagy by intra-tumoral delivery of membrane-fused mitochondria or Midiv-1 enhances sensitivity to doxorubicin in triple-negative breast cancer. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Mitochondrial Role in Oncogenesis and Potential Chemotherapeutic Strategy of Mitochondrial Infusion in Breast Cancer. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Metabolic resistance to the inhibition of mitochondrial transcription revealed by CRISPR-Cas9 screen. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Mitochondrial structure and function adaptation in residual triple negative breast cancer cells surviving chemotherapy treatment. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Crosstalk from non-cancerous mitochondria can inhibit tumor properties of metastatic cells by suppressing oncogenic pathways. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Drug induced mitochondrial dysfunction: Mechanisms and adverse clinical consequences. [2017]

7. Netherlands pubmed.ncbi.nlm.nih.gov

The Role of Therapeutic Drugs on Acquired Mitochondrial Toxicity. [2019]

8. England pubmed.ncbi.nlm.nih.gov

The significance of mitochondrial toxicity testing in drug development. [2013]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Developing In Vitro Models to Define the Role of Direct Mitochondrial Toxicity in Frequently Reported Drug-Induced Rhabdomyolysis. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Strategies to reduce late-stage drug attrition due to mitochondrial toxicity. [2013]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Mitochondrial fusion provides an 'initial metabolic complementation' controlled by mtDNA. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Mitochondrial functional complementation in mitochondrial DNA-based diseases. [2009]

13. United States pubmed.ncbi.nlm.nih.gov

Antisense Oligonucleotide-Mediated Silencing of Mitochondrial Fusion and Fission Factors Modulates Mitochondrial Dynamics and Rescues Mitochondrial Dysfunction. [2022]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Intramitochondrial transfer and engineering of mammalian mitochondrial genomes in yeast. [2019]

15. England pubmed.ncbi.nlm.nih.gov

Selective removal of deletion-bearing mitochondrial DNA in heteroplasmic Drosophila. [2023]