Nitric oxide (NO) and peroxynitrite (ONOO-) are cytotoxic species produced in various forms of inflammation. Recent studies have inplicated the crucial role of NO and peroxynitrite in the pathogenesis of various forms of neurodegenerative disorders, including allergic encephalomyelitis (EAE). Inotek Corporation is developing a unique class of compounds, mercaptoalkylguanidines (MAGs), which: 1) inhibit the inducible isoform of nitric oxide synthase (iNOS), an enzyme which is overexpressed in various forms of inflammation and produces cytotoxic amounts of NO, and 2) scavenge peroxynitrite, a reactive, toxic oxidant produced in inflammation, Inotek's lead MAG compound, guanidinoethyldisulfide (GED), requires demonstration of efficacy in a clinically relevant experimental model of EAE in order to justify its commercialization as a novel agent for the treatment of multiple sclerosis.
The Specific Aim of this Phase I SBIR is to establish whether GED prevents the course of the disease development in a murine experimental model of allergic encephalomyelitis. Demonstration that GED had commercial feasibility will permit application for Phase II SBIR funding to support: Pre-clinical pharmaceutical testing, advanced toxicity determinations, pathology, stability, pharmacokinetics, in vivo efficacy, Investigational Drug Application to the FDA and Phase I Clinical Trial.
The market for novel, effective therapy for multiple sclerosis is enormous. There are no mechanism-based therapies for MS. Recent breakthroughs in the field of free radicals offered a new therapeutic possibility by targeting nitric oxide and peroxynitrite.
