Radiation countermeasures for hematopoietic acute radiation syndrome: growth factors, cytokines and beyond

Abstract

Purpose: The intent of this article is to report the status of some of the pharmaceuticals currently in late stage development for possible use for individuals unwantedly and acutely injured as a result of radiological/nuclear exposures. The two major questions we attempt to address here are: (a) What medicinals are currently deemed by regulatory authorities (US FDA) to be safe and effective and are being stockpiled? (b) What additional agents might be needed to make the federal/state/local medicinal repositories more robust and useful in effectively managing contingencies involving radiation overexposures?

Conclusions: A limited number (precisely four) of medicinals have been deemed safe and effective, and are approved by the US FDA for the 'hematopoietic acute radiation syndrome (H-ARS).' These agents are largely recombinant growth factors (e.g. rhuG-CSF/filgrastim, rhuGM-CSF/sargramostim) that target and stimulate myeloid progenitors within bone marrow. Romiplostim, a small molecular agonist that enhances platelet production via stimulation of bone marrow megakaryocytes, has been recently approved and indicated for H-ARS. It is critical that additional agents for other major sub-syndromes of ARS (gastrointestinal-ARS) be approved. Future success in developing such medicinals will undoubtedly entail some form of a polypharmaceutical strategy, or perhaps novel, bioengineered chimeric agents with multiple, radioprotective/radiomitigative functionalities.

Keywords: Animal models; animal rule; countermeasures; cytokines; food and drug administration; growth factors; irradiation.