Efficacy of RAP-536 in Alleviating Anemia in Myelodysplastic Syndrome: Insights from a Murine Model

Myelodysplastic syndrome (MDS) is identified as a condition with ineffective blood cell production, where patients may endure prolonged periods but are at risk of severe anemia or progression to acute leukemia. The standard treatment options involve chemotherapy and blood transfusions, with many therapies focusing on the EPO pathway to manage anemia. However, there is a noted concern regarding the increased mortality risk associated with EPO and its recombinant forms due to their potential to accelerate tumor growth and cause thromboembolic events. Lenalidomide has demonstrated effectiveness in lowering the need for red blood cell transfusions, particularly for MDS patients with a specific genetic abnormality.

The study introduces RAP-536, a protein derived from the activin receptor type IIB (ActRIIB) that can bind TGF-β ligands and inhibit their signaling. This research aims to assess RAP-536's potential in enhancing hematopoiesis in an MDS mouse model. The experiment involved NUP98-HOX13 transgenic mice, which were administered either a placebo or RAP-536 at a dosage of 10 mg/kg twice weekly. Concurrently, wild-type mice were used as controls.

At the beginning of the study, the male transgenic mice exhibited a significant reduction in red blood cell count, hematocrit, and white blood cell count when compared to the controls. Female transgenic mice showed similar trends, with a significant decrease in white blood cells. After one month of treatment, male mice given RAP-536 experienced a substantial increase in red blood cell count, hemoglobin, and hematocrit. Female mice also saw an increase, although less pronounced.

After a four-month treatment period, both male and female transgenic mice treated with RAP-536 showed a significant rise in red blood cell count, hemoglobin, and hematocrit. The white blood cell count remained lower in transgenic mice compared to controls, but no significant differences were observed between RAP-536 and placebo-treated groups.

The findings indicate that RAP-536, by utilizing a distinct pathway from EPO, could be a promising new approach for treating severe anemia in MDS patients and those with related blood disorders.