Rapid and Robust Mobilization of Hematopoietic Stem Cells With MGTA-145: A Truncated Protein Variant of the Chemokine CXCL2
Dwight Morrow
VP Preclinical Development, Magenta Therapeutics
Significant needs remain for patients living with autoimmune diseases, blood cancers, and rare genetic diseases. Bone marrow transplant is a potential cure for many, but its high risks, toxic side effects and complexity prevent many patients from being able to benefit. Obtaining sufficient hematopoietic stem cells is a critical part of the transplant process. Magenta is developing MGTA-145 specifically to improve the efficiency and efficacy of hematopoietic stem cell mobilization and transplant for all potential donors. MGTA-145 is a truncated variant of the naturally occurring immunomodulatory chemokine CXCL2. Chemokines are small protein ligands (8 – 10 KDa) that bind to G-protein couple receptors. MGTA-145 binds and activates its cognate receptor CXCR2 to elicit a variety of intracellular signaling pathways that regulate diverse biological functions including chemotaxis, inflammation and angiogenesis. Preclinical studies have demonstrated that MGTA-145 when administered in combination with the CXCR4 inhibitor, AMD3100, results in a synergistic increase in mobilization of HSCs in both mice and non-human primates, particularly long-term engraftable HSCs. MGTA-145, in combination with AMD3100, may offer a more robust and safer alternative for autologous and allogeneic transplant, including diseases such as sickle cell disease (SCD) and multiple sclerosis (MS) where standard of care is contraindicated or associated with adverse events.