Mitochondrial Transplant for Stroke

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Washington

Disqualifiers: Mitochondrial disease, Hemodynamic instability, others

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

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals who have experienced a stroke. The treatment, called Autologous Mitochondrial Transplant, involves infusing healthy mitochondria—tiny cell components that produce energy—into the brain's blood vessels to aid in the recovery of damaged brain tissue. It targets those eligible for standard stroke treatments, such as endovascular thrombectomy, and may also benefit individuals with certain complications following a brain aneurysm. Participants must be able to consent to the trial or have someone provide consent on their behalf. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance recovery options for stroke patients.

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 this mitochondrial transplant is safe for stroke patients?

Research has shown that treatments using a person's own mitochondria are promising in terms of safety. In a previous study, patients who received this treatment for acute ischemic stroke reported only a few side effects, suggesting the treatment is generally well-tolerated. Additionally, many animal studies have demonstrated that adding healthy mitochondria (tiny parts of cells that produce energy) to damaged tissue can aid in repair without causing harm. These findings suggest that safety risks for humans might be low.

Although large human studies are limited, evidence from smaller studies and animal research supports the potential safety of this treatment for humans. Overall, it appears promising, but further research is needed to fully confirm its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for stroke, which often include clot-busting drugs like tPA or surgical interventions, the autologous mitochondrial transplant offers a novel approach by using the body's own mitochondria. Researchers are excited about this treatment because it involves endovascular infusion, directly delivering healthy mitochondria to damaged brain cells, potentially enhancing their recovery and energy production. This unique mechanism could help repair stroke-affected areas more effectively, potentially leading to faster and more complete recovery compared to traditional methods.

What evidence suggests that autologous mitochondrial transplant might be an effective treatment for stroke?

Research has shown that using a person's own healthy mitochondria might help treat sudden strokes. In this trial, participants will receive an endovascular infusion of their own mitochondria, a process known as Autologous Mitochondrial Transplantation. Early studies indicate that this treatment involves placing these energy-producing cell parts into the brain's blood vessels. These mitochondria may help reduce stroke-induced damage. Initial findings suggest that this method could improve recovery by protecting brain tissue. Although the treatment is still under study, early results are promising for reducing brain damage after a stroke. ^{1 2 4 6 7}

Who Is on the Research Team?

Melanie S Walker, MD

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

This trial is for patients eligible for endovascular thrombectomy due to acute large vessel occlusion or angioplasty after subarachnoid hemorrhage. Candidates must be stable enough for standard reperfusion treatment and able to give consent. Those with mitochondrial diseases, unable to undergo MRI, or hemodynamically unstable cannot participate.

Inclusion Criteria

Subjects for whom there is likely to be enough time to obtain meaningful consent from patient or legally-authorized representative

I am a candidate for a special procedure to treat brain vessel narrowing after a specific type of stroke.

I am a candidate for a procedure to remove a large blood clot in my vessel.

Exclusion Criteria

You cannot have a brain MRI scan.

I cannot undergo standard stroke treatments due to my unstable condition.

You have a known mitochondrial disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo standard-of-care endovascular reperfusion therapy with concurrent autologous mitochondrial transplant

1 day

1 visit (in-person)

Immediate Follow-up

Participants are monitored for severe adverse vascular events and systemic adverse events immediately post-mitochondrial infusion

Up to 7 days

Daily monitoring (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including reduction of infarct volume

Up to 7 days

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Mitochondrial Transplant

Trial Overview The study tests the infusion of a patient's own healthy mitochondria into brain vessels affected by ischemia during standard endovascular reperfusion therapy. The goal is to see if this can help recover brain tissue that isn't getting enough blood flow due to stroke.

How Is the Trial Designed?

Group I: Transplantation Experimental Treatment 1 Intervention

Endovascular infusion

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Published Research Related to This Trial

Mitochondrial dysfunction is linked to brain impairments after stroke, and recent studies suggest that healthy mitochondria play a crucial role in neuroprotection and recovery following ischemic stroke.

Mitochondrial transplantation, particularly through stem cells, shows promise as a novel therapeutic strategy by replacing damaged mitochondria with healthy ones, potentially improving recovery outcomes after ischemic stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondrial Transfer as a Therapeutic Strategy Against Ischemic Stroke. Chen, W., Huang, J., Hu, Y., et al.[2021]

Artificial mitochondrial transfer/transplant (AMT/T) has emerged as a promising therapeutic approach over the last 40 years, particularly for repairing cellular damage and treating organ ischemia-reperfusion injury.

Despite advancements, critical questions remain regarding the optimal methods for isolating mitochondria and selecting appropriate tissue or cell sources, which are essential for advancing clinical applications of AMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancing mitochondria as a therapeutic agent. Caicedo, A., Singh, KK.[2023]

Mitochondrial transplantation shows promise as a potential treatment for various diseases related to mitochondrial dysfunction, including neurodegenerative diseases and cardiovascular conditions.

The review outlines key aspects of mitochondrial transplantation, including natural transfer mechanisms, isolation processes, and methods of transplantation, highlighting its innovative potential for treating diseases that currently lack effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic applications of mitochondrial transplantation. Ulger, O., Kubat, GB.[2022]

Mitochondrial autophagy plays a crucial role in protecting cells during cerebral stroke by selectively removing damaged mitochondria, which helps maintain cellular balance.

Dysfunction of mitochondria during a stroke can lead to various harmful processes, including oxidative stress and apoptosis, highlighting the importance of understanding mitochondrial autophagy for developing potential treatments for ischemic stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Research Progress on the Mechanism of Mitochondrial Autophagy in Cerebral Stroke. Lei, L., Yang, S., Lu, X., et al.[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]

Mitochondrial transplantation is emerging as a promising therapeutic approach for ischemic stroke, addressing mitochondrial dysfunction and ATP depletion, which are critical issues following a stroke.

The review highlights both in vitro and in vivo studies that support the efficacy of mitochondrial transplantation, while also discussing pharmacological methods to enhance this treatment and the challenges that may arise in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Updated Review of Mitochondrial Transplantation as a Potential Therapeutic Strategy Against Cerebral Ischemia and Cerebral Ischemia/Reperfusion Injury. Huang, H., Oo, TT., Apaijai, N., et al.[2023]

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]

Mitochondrial transplantation is a promising new treatment for disorders related to ischemia/reperfusion, showing potential for clinical efficacy in human patients.

The procedure is straightforward and can be administered quickly through direct injection or vascular infusion, making it a practical option for therapeutic intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondrial transplantation: From animal models to clinical use in humans. McCully, JD., Cowan, DB., Emani, SM., et al.[2018]

Mitochondrial replacement techniques have shown promising safety and efficacy in previous studies, indicating their potential for clinical use.

However, significant challenges exist in implementing these techniques, highlighting the need for international consensus on regulatory frameworks to address scientific and ethical concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondrial replacement approaches: challenges for clinical implementation. Klopstock, T., Klopstock, B., Prokisch, H.[2018]

Mitochondrial transplant therapy (MTT) did not increase inflammation and significantly reduced the amount of non-contractile tissue in injured muscles compared to controls, suggesting a beneficial effect on muscle repair.

MTT-treated mice showed improved recovery of muscle mass and function, reaching control levels by 14 days post-injury, while PBS-treated mice did not achieve similar recovery, indicating that MTT can enhance muscle regeneration after injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondria transplant therapy improves regeneration and restoration of injured skeletal muscle. Alway, SE., Paez, HG., Pitzer, CR., 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/NCT04998357

Autologous Mitochondrial Transplant for Cerebral Ischemia The investigators propose to infuse healthy autologous mitochondria into cerebral vessels supplying brain tissue experiencing ischemia in patients who undergo ...

3. ahajournals.org ahajournals.org/doi/10.1161/SVIN.122.000644

Intraarterial Transplantation of Mitochondria After Ischemic ... Transplantation of autologous mitochondria into ischemic tissue may mitigate injury caused by ischemia and reperfusion.

4. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/0271678X241305230

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 ...

5. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-023-02759-0

Exogenous mitochondrial transplantation improves survival ... Our study tests the hypothesis that MTx can improve the outcomes after resuscitation from a severe ischemic injury such as a CA. We focus on ...

6. wms-site.com wms-site.com/alert-on-mitochondria/1029-use-of-mitochondrial-transplantation-for-stroke

Autologous Mitochondrial Transplant for Cerebral Ischemia Based on many preclinical studies in animals, damage caused by ischemia can be reversed after infusing healthy mitochondria into injured tissues.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/?term=Sam%20Hs%20Levy%5BAuthor%5D&cauthor=true&cauthor_uid=39628322

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 ...