Validation of Novel Therapeutic Approach for Cryptococcal Meningitis

Validation of a Novel Therapeutic Approach for Cryptococcal Meningitis PILadShivanand and McCabeAaron Project Summary When Cryptococcus is manifested as cryptococcal meningitisCMit creates a large burden of mortality and morbidity to the patient and is very difficult for the clinician to treatThere are now an estimatedUS cases andcases of CM worldwide annuallywith estimated mortality ofper yearCM is caused when Cryptococcus neoformansa basidiomycete fungal pathogeninvades the central nervous systemCNSIt is seen most commonly in immunocompromised patientssuch as those with HIV or post organ transplantCurrent treatments include anti fungal agents that have limited effectiveness in penetrating the CNS and various systemic side effectsReduction in pathogen burden within the firstdays of therapy is the best predictor of reduced morbidity and mortalityMinnetronixa medical device development and manufacturing companyproposes this Phase II STTR in collaboration with experts from the Infectious Diseases and Neurosurgery Departments at Duke UniversityPhase I demonstrated the dramatic results of Neurapheresisa cerebrospinal fluidCSFprocessing platformwith rapid clearance of organisms both in vitro and in vivoin a rabbit CM modelPhase II will optimize and validate a tailored human system to target and rapidly remove Cneoformans from the CSFSpecific Aimwill demonstrate in vivo reduction of CSF fungal colony forming units and Cryptococcal antigen in a pivotal animal study using a validated rabbit CM modelSpecific Aimwill demonstrate the computational fluid and flow dynamics of Cryptococcal clearance using a bench top human cranial spinal modelSpecific Aimwill focus on completing development of a tailored human Neurapheresis system for reduction of CSF infection burdenNeurapheresis is an innovativenew therapeutic option that provides direct access to the CSF and creates active circulationcombined with targeted pathogen removalThis treatment is intended to be complementary and does not replace standard of careSOCinterventions with systemicintravenous antifungal regimensSuccessful completion of this Phase II STTR will provide Minnetronix with the ability to complete development of a GLP quality system for the treatment of CMConcurrent regulatoryclinical planningand reimbursement work will be conducted to prepare for an investigational device exemptionIDEapplication at the end of Phase IIThe long term goal of the project is to develop a novel therapeutic approach that rapidly reduces CSF fungal burden and translates to reduced morbidity and mortality for CM patients worldwide