Role of HBI-002, an orally administered gasotransmitter, in ischemic stroke

DESCRIPTION provided by applicant The objective of the proposed project is to investigate the potential of the gasotransmitter carbon monoxide CO as a neuroprotective agent in acute ischemic stroke AIS using a novel oral formulation of CO HBI Numerous studies both in vitro and in vivo demonstrate that CO has cytoprotective properties through anti oxidant anti inflammatory and anti apoptotic processes In five studies in three independent laboratories researchers found that the heme oxygenase HO CO pathway provides neuroprotection in animal models of AIS In four of these studies exogenous administration of CO which has been shown to up regulate HO reduced cerebral infarct size improved behavioral scores and increased blood flow to the infarct border zone in experimental stroke These independent studies provide compelling support for a potential beneficial role for the use of CO in the treatment of AIS However CO administration strategies have been limited to inhalation and intravenous approaches that carry inherent risks of safety and toxicity HBI an aqueous carboxylipid protein liquid formulation is being developed for the treatment of AIS The administration of a defined dose of CO delivered by oral administration of HBI obviates the problems associated with previously studied inhaled or intravenously administered carrier metal CO HBI comprises a water based solution containing CO Proof of concept manufacture of HBI has been demonstrated Pharmacokinetic and pharmacodynamic studies in rats and in two adult healthy volunteers have demonstrated proof of concept feasibility tolerability and bioavailability The next step in development is to demonstrate that CO delivered via the oral administration of HBI improves outcome in appropriate AIS animal models and to further understand the potential mechanisms of neuroprotection PUBLIC HEALTH RELEVANCE This proposal is intended to support research evaluating whether HBI an oral carbon monoxide CO therapeutic can improve outcomes in animal models of Acute Ischemic Stroke AIS If successful the project will provide proof of concept for further development of HBI in AIS as a promising therapeutic to improve neurological outcomes in this devastating disease