Mitochondria Transplantation for Heart Ischemia

Overseen By Breanna Piekarski, RN, BSN

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Boston Children's Hospital

Disqualifiers: Mitochondria disorders

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

16 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators propose a robust therapeutic intervention to ameliorate myocardial ischemia/ reperfusion injury and significantly decrease morbidity and mortality in patients requiring extracorporeal membrane oxygenation (ECMO), by direct injection of autogeneic mitochondria into the ischemic myocardium.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is mitochondrial transplantation safe for humans?

Research shows that mitochondrial transplantation, using a person's own healthy mitochondria, is generally safe in humans and animals, with no immune reactions or heart rhythm problems reported. It has been tested for heart and other organ conditions, showing promise in improving cell function and survival. ^{1 2 3 4 5}

How is the treatment of Autologous Mitochondria Transplantation unique for heart ischemia?

Autologous Mitochondria Transplantation is unique because it involves transplanting healthy mitochondria from the patient's own body into damaged heart tissue to restore energy production and improve heart function, unlike traditional treatments that do not directly replace damaged cellular components. ^{2 3 4 6 7}

Research Team

Sitaram Emani, MD

Principal Investigator

Boston Children's Hospital

Eligibility Criteria

This trial is for pediatric cardiology patients under 18 years old who are on ECMO (a life support machine) and have concerns about heart muscle damage due to poor blood flow. It's not open to those with known mitochondrial disorders.

Inclusion Criteria

I am in the ICU for heart-related issues.

My child is under 18 and on ECMO for heart support.

Exclusion Criteria

I have a diagnosed mitochondrial disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Autologous mitochondria are injected into ischemic areas of the myocardium during surgical or catheterization procedures

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including the ability to be separated from ECMO support and improvement in ventricular function

1 week - 1 month

Treatment Details

Interventions

• Autologous Mitochondria Transplantation

Trial Overview The study is testing a new procedure where mitochondria, the energy-producing parts of cells, are taken from the patient's own body and injected into their heart muscle that has been damaged by poor blood flow.

Participant Groups

Group I: Autologous mitochondria injection Experimental Treatment 1 Intervention

All subjects will have autologous mitochondria injected into ischemic areas of the myocardium (via injection or infusion).

Autologous Mitochondria Transplantation is already approved in United States for the following indications:

Approved in United States as Autologous Mitochondria Transplantation for:

• Myocardial ischemia/reperfusion injury in patients requiring ECMO

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Findings from Research

In a study using swine models, autologous mitochondrial transplantation via intracoronary delivery was found to be safe and effectively targeted to the heart, leading to improved coronary blood flow.

This method significantly enhanced myocardial function and reduced infarct size after ischemia-reperfusion injury, indicating its potential as a therapeutic approach for heart damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Biological Strategy for Myocardial Protection by Intracoronary Delivery of Mitochondria: Safety and Efficacy. Shin, B., Saeed, MY., Esch, JJ., et al.[2020]

Transplanting autologous mitochondria (from the patient's own body) into the heart during early reperfusion after ischemia significantly improves heart function and cell survival, enhancing recovery after blood flow restoration.

The transplanted mitochondria not only boost energy production and cellular health but also do so without causing immune reactions or arrhythmias, suggesting a safe and effective therapeutic approach for ischemic heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondrial transplantation for therapeutic use. McCully, JD., Levitsky, S., Del Nido, PJ., et al.[2020]

Mitochondrial transplantation can effectively replace damaged mitochondria in cells with healthy ones from the patient's own body, showing potential benefits for treating organ ischemia-reperfusion injury.

The safety and efficacy of this approach have been validated through various studies, including cell cultures, large animal models, and a first human clinical trial, indicating its broad applicability across different cell types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondrial transplantation for organ rescue. McCully, JD., Del Nido, PJ., Emani, SM.[2022]

Transplanting autologous mitochondria into ischemic brain tissue can significantly improve cell viability and reduce injury from stroke, as shown in murine models where mitochondria integrated into brain cells and increased ATP levels.

Using focused ultrasound to activate microbubbles enhances the delivery of mitochondria by safely opening the blood-brain barrier, improving treatment efficacy without causing bleeding complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraarterial Transplantation of Mitochondria After Ischemic Stroke Reduces Cerebral Infarction. Norat, P., Sokolowski, JD., Gorick, CM., et al.[2023]

Transplanting autologously derived mitochondria into the heart before reperfusion significantly reduced heart damage and improved recovery after ischemia in New Zealand White rabbits, with infarct size decreasing from 34.2% to 7.9%.

The procedure was safe, showing no associated arrhythmias, and helped restore normal heart function quickly, enhancing energy production and cell survival in the heart tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury. Masuzawa, A., Black, KM., Pacak, CA., et al.[2022]

Mitochondrial transplantation involves introducing isolated mitochondria into damaged heart tissue, showing promising therapeutic effects in animal studies with ischemic heart damage.

The procedure is based on the idea that these exogenous mitochondria can enter heart cells and restore energy production, although this hypothesis raises questions due to known issues with mitochondrial function in high calcium environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondrial Transplantation: A Critical Analysis. Chernyak, BV.[2021]

Mitochondrial transplantation shows promise for treating heart damage from ischemia-reperfusion injury by potentially replacing damaged mitochondria and restoring heart function.

However, challenges such as poor internalization and survival of transplanted mitochondria need to be addressed to enhance the effectiveness of this therapy, highlighting the importance of optimizing mitochondrial sources and transplantation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What can we do to optimize mitochondrial transplantation therapy for myocardial ischemia-reperfusion injury? Liu, Q., Liu, M., Yang, T., et al.[2023]

References

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

A Novel Biological Strategy for Myocardial Protection by Intracoronary Delivery of Mitochondria: Safety and Efficacy. [2020]

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

Mitochondrial transplantation for therapeutic use. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Mitochondrial transplantation for organ rescue. [2022]

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

Intraarterial Transplantation of Mitochondria After Ischemic Stroke Reduces Cerebral Infarction. [2023]

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

Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury. [2022]

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

Mitochondrial Transplantation: A Critical Analysis. [2021]

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

What can we do to optimize mitochondrial transplantation therapy for myocardial ischemia-reperfusion injury? [2023]