GLYCOMIRA, LLC — Department of Health and Human Services SBIR Phase I: NIAID

Description

PROJECT SUMMARY This proposal aims to develop a therapeutic capable of preventing and treating the severe sinus inflammation associated with chronic rhinosinusitis CRS CRS is a debilitating inflammatory disease of the sinuses that impacts over million Americans and substantially diminishes the quality of life and productivity of affected patients From to the total US health care expenditure to treat patients with CRS increased from $ to $ billion USD with a corresponding rise in surgical treatment for those patients who fail current medical management CRS is characterized by massive inflammatory cell infiltration and increased cytokine chemokine production Therapy development should therefore be focused on inhibiting the mechanisms underlying the initiation of these inflammatory responses with the ability to be delivered efficiently by high volume saline irrigation known to improve mucosal penetration GlycoMira Therapeutics Inc GMTI is developing a glycosaminoglycan based anti inflammatory compound GM for CRS that is polyanionic giving it excellent solubility in saline Our work has shown that GM is safe efficiently penetrates the sinuses and effectively prevents acute sinus inflammation by blocking neutrophil activation and mast cell infiltration into the sinus mucosa GM additionally inhibits important early pro inflammatory signaling molecules such as Toll like receptors and selectins resulting in decreased inflammatory mediator production Based on our findings we hypothesize that GM can prevent the development and progression of CRS by inhibiting inflammatory cell chemotaxis and activation within the sinuses thereby reducing inflammation Chemokines RANTES and eotaxin are elevated in patients with CRS and are important in recruiting mast cells early effector cells and eosinophils late effector cells which favor a therapeutic resistant state of inflammation We will first test our hypothesis Aim by determining whether GM can inhibit chemokine mediated activation of human mast cells eosinophilic cells and chemokine receptor knockdown cells negative control measuring intracellular calcium flux proliferation and chemotaxis in the absence and presence of recombinant chemokine These studies will provide inflammatory mechanism focused results for therapy translation to CRS We will then test the feasibility of GM to prevent and treat CRS in vivo using a mouse model of CRS Aim Applying two dosing regimens we will approach this goal by administering GM prior to and after establishing chronic sinus inflammation Sinus tissues will be examined for histological characteristics inflammatory cell infiltration secretory cell hyperplasia mucous secretion and mucosa thickening and tissue inflammatory biomarkers mast cell tryptase eosinophil myeloperoxidase RANTES and eotaxin These studies will provide crucial preclinical data supporting GM as a therapeutic aimed at preventing and treating sinus inflammation in patients with CRS moving towards commercialization in a market with tremendous unmet needs to improve the lives of millions of Americans PROJECT NARRATIVE Chronic rhinosinusitius CRS is a debilitating disease of sinus inflammation that substantially diminishes the quality of life and productivity of over million Americans resulting in an annual economic burden of $ billion USD The currently available therapies for CRS fail to control the inflammation in of every patients leaving surgery as the alternative treatment We have developed a compound that efficiently coats the sinuses and effectively inhibits multiple inflammatory events and factors underlying the mechanisms that favor inflammation Having important implications for patients physicians and public policymakers alike we will develop this compound into a therapeutic that is capable of preventing and treating CRS improving the lives of millions of Americans