Autologous Mitochondrial Transplant for Cerebral Ischemia

Stroke is one of the leading causes of morbidity and mortality worldwide. More than 80% of strokes are the result of ischemia caused by blockage of one or more cerebral arteries. Lack of blood supply starves brain cells of necessary glucose and oxygen, and disturbs cellular homeostasis, eventually resulting in neuronal death.

Mitochondria are tiny organelles present in nearly all types of human cells and are vital to our survival. Much like a battery, they generate most of our adenosine triphosphate (ATP), the energy currency of the cell. Mitochondria are also involved in other tasks, such as signaling between cells and cell death. All these functions can be impaired during ischemia because of the damage caused to mitochondria.

Based on many preclinical studies in animals, damage caused by ischemia can be reversed after infusing healthy mitochondria into injured tissues. An ongoing clinical trial in human hearts at Boston Children's Hospital has also demonstrated that transplanting autologous mitochondria via infusion or direct injection is well-tolerated and safe.

The investigators at the University of Washington are recruiting subjects for a first-in-human-brain trial to confirm the safety of autologous mitochondrial transplant during brain ischemia. The transplantation will be performed within the same procedure as the clinically indicated reperfusion treatment.

During standard-of-care endovascular treatment for cerebral ischemia, the investigators will obtain a very small biopsy from the muscle tissue adjacent to our surgical access site. Muscle tissue will be processed at bedside to extract the autologous mitochondria as performed in prior human cardiac trial and validated in animal studies. The endovascular treatment proceeds without disruption as clinically indicated, and the mitochondria are infused into the brain artery via micro-catheter during reperfusion.

Inclusion criteria

• Eligible for endovascular thrombectomy to treat acute large vessel occlusion
• Eligible for angioplasty (microcatheter-based balloon/mechanical and chemical angioplasty) to treat acute cerebral vasospasm after aneurysmal subarachnoid hemorrhage
• Subjects for whom there is likely to be enough time to obtain meaningful consent from patient or legally-authorized representative

Exclusion criteria

• Unable to receive a brain MRI scan
• Known mitochondrial disease
• Hemodynamically unstable patients in whom standard of care endovascular reperfusion treatment cannot safely be performed or completed