Novel 2B9F Peptide Achieves Complete Survival in Lethal Murine Radiation Syndrome, Outperforms Romiplostim

Hematopoietic Acute Radiation Syndrome (H-ARS) presents a critical challenge following radiation exposure, often leading to severe hematopoietic system damage and high mortality. Current therapeutic options are limited in both variety and efficacy, failing to ensure durable recovery. Thrombopoietin (TPO) is a key regulator of hematopoiesis, stimulating megakaryopoiesis and stem cell proliferation. Developing stable, low-immunogenicity TPO-mimetics like 2B9F could offer a superior strategy to enhance hematopoietic recovery and survival in radiation emergencies.

Researchers developed 2B9F, a novel thrombopoietin-mimetic peptide, engineered for enhanced stability and low immunogenicity. Its efficacy was evaluated in a lethal murine irradiation model. Mice received a single subcutaneous dose of 2B9F post-exposure, with romiplostim serving as a comparator. Primary endpoints included overall survival, recovery of peripheral blood counts, and bone marrow nucleated cells. Functional hematopoietic stem cell (HSC) expansion, in vitro clonogenic potential, and in vivo competitive repopulation capacity were also assessed. Mechanistic studies investigated transcriptional modulation of apoptosis and cell-cycle regulators.

A single subcutaneous dose of 2B9F administered post-exposure achieved complete survival in a lethal murine irradiation model, significantly surpassing the efficacy of the clinically approved agent romiplostim.

Treatment with 2B9F accelerated the recovery of peripheral blood counts and bone marrow nucleated cells, expanded functional HSCs, and enhanced both in vitro clonogenic potential and in vivo competitive repopulation capacity. Mechanistic studies revealed that 2B9F promoted HSC quiescence and survival through transcriptional modulation of apoptosis and cell-cycle regulators. Importantly, a single low dose of 2B9F also conferred durable protection, mitigating delayed bone marrow suppression for up to six months post-irradiation. These findings highlight 2B9F's potent radioprotective effects.