Mitochondrial Augmentation Technology: Harnessing mitochondria to improve cellular functionality

Mitochondrial Augmentation Technology (MAT) is a platform technology designed for enriching cells with healthy exogenous mitochondria.

To address the underlying cause of Primary mtDNA disorders, delivery and persistence of exogenous mtDNA is necessary in order to achieve efficacy in diseased target organs.

Our first product is composed of hematopoietic stem and progenitor cells (HSPCs) enriched with allogeneic mitochondria. While maintaining their stemness state, HSPCs are quiescent and mostly use glycolysis to produce ATP, yet they require high levels of mitochondrial activity to differentiate and proliferate into the various hematopoietic lineages. Using allogenic placental-derived mitochondria and novel analytical methods, we are exploring parameters affecting persistence of exogenous mtDNA after MAT and the effect of co-existence of 2 different haplogroups on cell functionality. For this purpose we have generated a bank of qualified mitochondria of numerous haplogroups and are using these to enrich HSPCs with mitochondria of multiple haplogroups. As a model for mitochondrial diseases, we are using patient-derived Lymphoblastic Cell Lines (LCL) with different heteroplasmy levels, that allows us to study the ability of MAT to rescue disease phenotype. Single-cell methodologies such as ATP-dependent protein synthesis have demonstrated that higher levels of augmentation enable higher protein synthesis levels.

In addition, we are intrigued by the recent evidence suggesting that immunological factors play a significant role in PMD pathology even in the absent of clear hematological or immunological manifestations. We are currently exploring mechanisms by which MAT using HSPCs may treat PMD with significant and durable benefit by altering the immune system.