Enriching patient's hematopoietic & progenitor cells with healthy mitochondria isolated from
a healthy donor
Manufacturing of a qualified mitochondria product derived from healthy donor cells
Patient’s hematopoietic stem cells are mobilized to the peripheral blood to allow cell collection by apheresis
Autologous CD34+ HSPCs are selected from the apheresis product
Selected cells are enriched with healthy mitochondria
The mitochondrially augmented cells are then reinfused back to patient’s bloodstream
* MAT is an investigational therapy that is undergoing clinical study to verify its safety and effectiveness.
Additional information can be found on ClinicalTrials.gov.
Primary Mitochondrial Diseases (PMDs) are a heterogeneous group of disorders caused by mutations or deletions in nuclear or mitochondrial DNA (mtDNA), displaying a wide range of severity and phenotypes. These complex, multi-systemic and rare group of diseases occur as a result of mitochondrial dysfunction.
PMDs can be inherited (mitochondrial inheritance) or non-inherited (de-novo). The latter also include rare pediatric diseases caused by a mutation or deletion in mtDNA, which develop into a systemic multi organ disease and can be fatal. Currently, there are no approved disease modifying drugs for mitochondrial diseases and patients are treated with supportive care only.
Secondary mitochondrial diseases, or diseases associated with mitochondrial dysfunction. Amassing evidence has demonstrated the involvement of mitochondrial dysfunction in a variety of degenerative disorders. This includes more common diseases of the bone marrow, such as myelodysplastic syndrome (MDS), as well as diseases of other tissues, for example neurocognitive disorders such as Alzheimer's disease. Preliminary preclinical evidence suggests that mitochondrial augmentation may benefit clinically relevant aspects of these disorders.
Beyond HSPCs: Mitochondrial augmentation of additional cell types.
While Minovia's primary focus has been augmentation of HSPCs, we are exploring the potential benefit of augmentation of other mitochondrially exhausted cell types. For example, to treat hematopoietic and solid tumors, CART and TILs have been used in the past decade. However, one major limitation is the durability of effect due to metabolic exhaustion of cells. We are actively exploring the potential benefit MAT may provide additional cell therapies under development.
Minovia is currently evaluating the MAT platform to treat both inherited and non-inherited primary mtDNA diseases.
First generation (Syngeneic mitochondria, MNV-101): In our first clinical study of MAT, Pearson Syndrome patients were treated with autologous HSPCs enriched with healthy, functional mitochondria derived from a maternal blood unit. This personalized therapy was developed with the potential to treat only non-inherited mitochondrial disorders, and has shown a favorable safety and efficacy profile in a phase I/II clinical trial and in compassionate use cases for a number of disorders. This was published in Science Translational Medicine.
Second generation (Allogeneic mitochondria, MNV-201): Our second generation investigational product is being developed with the potential to treat both inherited and non-inherited PMDs, as well as secondary disorders associated with mitochondrial dysfunction. Patients will be treated with autologous HSPCs augmented with allogeneic mitochondria harvested.
Our current focus is on non-inherited and inherited primary mitochondrial diseases:
Pearson Syndrome is an ultra-rare, fatal disease. Usually the main symptom at diagnosis is associated with the bone marrow, therefore HSPCs are the right modality to treat this disease. It is not inherited, allowing the mother to be a donor of healthy mitochondria to her child.
For patients affected with an inherited mitochondrial disease, an allogeneic source of healthy mitochondria will be used for MAT. For this purpose, we have chosen the placenta, a young, healthy, ephemeral organ rich in mitochondria. Feasibility and safety studies are conducted to test matching requirements of allogeneic mitochondria carrying different haplotypes to personalize the therapy.
The current clinical trial protocols assess a single treatment. We continue to follow up on all patients, monitoring specific biomarkers, as well as the patient’s well-being and overall clinical condition to make informed decisions about a potential need for redosing. Ongoing preclinical studies aim to assess durability of affect.
No. To date, none of the studies performed at Minovia suggest a requirement for matching between the donor mitochondria and recipient cells. Actually, the fact that mitochondria come from an unmatched donor is useful, in that it may allow tracking of persistence of the donor mitochondria over time.
Just as no mitochondrial matching is performed when an organ transplant is provided, or when a blood or platelet transfusion is performed, it is highly unlikely that an immune response will occur. No immune responses have been evident in any preclinical studies, even when mitochondria and recipient cells were unmatched. However, as a safety precaution, responses will be carefully monitored in any human studies.
We constantly strive to develop MAT to reach as many patients as possible, and are acutely aware of the unmet needs of many patients with diseases associated with mitochondrial dysfunction. Please do not hesitate to reach out to us; we will save your details and reach out as soon as possible.
No, the new generation of augmented cells utilizes a mitochondrial bank harvested from healthy donated placentae. Each patient treated will receive cells augmented from this preexisting bank.
While in the future we plan to open sites around the globe, currently treatment is only possible at Sheba Medical Center, the hospital performing our clinical trials.