Mitochondrial Augmentation as a Therapeutic Strategy in Bone Marrow Failure Disorders: From Pearson Syndrome to Myelodysplastic Syndrome

Mitochondrial dysfunction is increasingly recognized as a shared pathophysiological driver across bone marrow failure disorders. Pearson Syndrome and myelodysplastic syndrome (MDS) represent two distinct ends of this spectrum — the former a devastating pediatric disease caused by large-scale mitochondrial DNA deletions, the latter the most common acquired bone marrow failure disorder of aging — yet both present with sideroblastic anemia driven by impaired mitochondrial function in hematopoietic progenitors. This biological overlap is further underscored by the clinical observation that a high proportion of Pearson Syndrome patients develop MDS over time, suggesting a shared pathogenic axis amenable to a common therapeutic approach.

MNV-201, Minovia`s first-in-class cell therapy consisting of autologous hematopoietic stem cells enriched with allogeneic placental mitochondria, has demonstrated proof-of-concept in Pearson Syndrome. In our ongoing Phase 2 clinical trial, 2 of the first 4 treated patients showed meaningful improvement in growth, as measured by height SDS, comparing the year following treatment to the year prior — with correlated improvements in multi-organ function including renal and hepatic.

Building on this foundation, we investigated MNV-201 in MDS. Blood-based mitochondrial biomarkers demonstrate that MDS patients carry dysfunctional mitochondria. Pre-clinical studies demonstrated delayed leukemic progression and improved survival in an MDS animal model following mitochondrial augmentation, as well as improved engraftment and erythroid differentiation of MDS hematopoietic stem cells, both in vitro and in vivo.

In our ongoing Phase 1b study in low-risk MDS patients, MNV-201 has demonstrated a favorable safety and tolerability profile with preliminary signals of efficacy across 8 patients dosed to date. Collectively, these data position low-risk MDS as a mitochondrial disease addressable by augmentation therapy and support continued clinical development of MNV-201 across the bone marrow failure spectrum.