Mitigation of GI-ARS By Stabilizing Mucosal Membrane Integrity

1 MITIGATION OF GI-ARS BY STABILIZING MUCOSAL MEMBRANE INTEGRITY 2 3 PROJECT SUMMARY/ABSTRACT 4 Development of an effective medical countermeasure (MCM) against Gastrointestinal Acute Radiation 5 Syndrome (GI-ARS) is of the utmost public health priority. An effective GI-ARS MCM must significantly im- 6 prove survival of individuals with GI-ARS. Increased survival requires preservation and/or recovery of GI mu- 7 cosa barrier integrity. Several Maroon Biotech biocompatible amphiphilic block copolymers have proven to be 8 effective in preserving mammalian cell membrane integrity and in cell prolonging survival following exposure 9 to 40Gy Gamma IR (Co60 at 21% O2) under standard cell culture conditions. When administered Maroon’s 10 MP8803 was subcutaneously administered (i.e. single dose) after Gamma IR (Cs137, 12-14 Gy total body irradi- 11 ation) C57BL/6 mice at a timepoint of 24 hours post-IR (in an FDA intramural pilot test), these copolymers 12 were found effective in preventing GI epithelial barrier breakdown and significantly reducing clinical signs of 13 GI-ARS. The effectiveness was dose dependent. 14 The purpose of this project is to establish efficacy of these copolymer for increasing both 10-day and 15 30-day survivals as well as preserving gut barrier function in the well-established Medical College of Wiscon- 16 sin’s LD 50/7 PBI-bone marrow sparring rat model of GI-ARS. All animal testing with performed under the 17 supervision of Dr. Heather Himburg and performed in her laboratory. Determining 30 day survival benefit and 18 effective dose is critically important for determining the potential public health and military benefit of MP8803. 19 MP8800 (Maroon Biotech) is a peroxide-free, reduced polydispersity biocompatible cell membrane seal- 20 ing agent that has been independently tested. Studies will be conducted in a blinded fashion. If significant 30- 21 day survival benefit is identified, a FDA Pre-IND meeting with schedule to expedite further development. Ma- 22 roon’s MP8803 and other compositions are covered by pending PCT and US patient applications. 23 24