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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist young heart patients on ECMO (a machine supporting heart and lung function) who suffer heart damage from reduced blood flow. Researchers are testing Autologous Mitochondria Transplantation, which involves injecting mitochondria (tiny powerhouses inside cells) directly into the damaged heart area. This approach aims to reduce heart damage and improve recovery. Patients under 18 with heart issues while on ECMO in the Cardiac Intensive Care Unit may qualify. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to innovative treatments for heart damage.

Will I have to stop taking my current medications?

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

What prior data suggests that autologous mitochondria transplantation is safe for heart ischemia?

Research has shown that using a patient's own mitochondria for treatment is generally safe. In one study, no major side effects appeared when this method restored blood flow after a blockage, suggesting the treatment's safety for patients.

This approach has also aided children's heart muscle recovery when they required ECMO support, a life-saving treatment that uses a machine to take over the heart and lungs' work. No significant safety issues were reported in these cases.

Overall, the evidence suggests that using a patient's own mitochondria is a promising and safe option for treating heart-related conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for heart ischemia, which typically involves medications like beta-blockers, statins, or surgical procedures like angioplasty, autologous mitochondria transplantation offers a novel approach. This treatment is unique because it involves injecting a patient's own mitochondria directly into the ischemic areas of the heart muscle. Researchers are excited because this method promises to restore energy production at the cellular level, potentially rejuvenating heart tissue and enhancing cardiac function. This direct targeting of cellular energy deficits is a game-changer, offering hope for more effective and quicker recovery compared to traditional treatments.

What evidence suggests that autologous mitochondria transplantation might be an effective treatment for heart ischemia?

Research shows that using a patient's own healthy mitochondria could be a promising treatment for heart problems. Mitochondria function like tiny power plants in cells. In this trial, all participants will receive autologous mitochondria injections into ischemic areas of the myocardium. Studies have found that injecting these healthy mitochondria into damaged heart tissue can help repair the heart and boost its energy. This method effectively protects the heart when blood flow returns after a period of low oxygen, known as ischemia-reperfusion injury. By increasing the heart's energy and repairing tissue, this treatment might significantly reduce complications for people with heart issues. Overall, early evidence suggests that this approach could improve heart function and lower the risk of further heart damage. ^{1 2 4 6 7}

Who Is on the Research Team?

Sitaram Emani, MD

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11615905/

Autologous mitochondrial transplant for acute cerebral ... The results of a Phase 1 trial of autologous mitochondrial transplantation for the treatment of acute ischemic stroke during mechanical ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02851758

Study Details | NCT02851758 | Transplantation of ... The investigators propose a robust therapeutic intervention to ameliorate myocardial ischemia/ reperfusion injury and significantly decrease morbidity and ...

3. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06805-8

Exploring mitochondrial health and transplantation strategies ... This review explores the significant potential of mitochondrial transplantation (MT) in enhancing outcomes for DCD heart transplantation.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3625892/

Transplantation of autologously derived mitochondria protects ... Transplantation of autologously derived mitochondria provides a novel technique to protect the heart from ischemia-reperfusion injury.

5. answers.childrenshospital.org answers.childrenshospital.org/mitochondrial-transfer/

Mitochondrial transfer restores heart muscle — but how? Transferring mitochondria from a patient's healthy skeletal muscle to damaged, ischemic heart tissue has been shown to restore heart muscle, increase energy ...

6. jtcvs.org jtcvs.org/article/S0022-5223(17)30258-1/pdf

Autologous mitochondrial transplantation for dysfunction ... This report describes the use of mitochondrial autotransplantation for myocardial recovery in pediatric patients who require ECMO support as a result of.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0022522319316630

Preischemic autologous mitochondrial transplantation by ... We present the results of preischemic autologous mitochondrial transplantation by intracoronary injection for prophylactic myocardial protection in a model of ...