Co-Development of a Novel Anti-Sickling Therapy and Its Companion Diagnostic for Future Sickle Cell Disease Management

Abstract In this Small Business Innovation ResearchSBIRPhase I projectFunctional Fluidics proposes to develop a novel anti sickling anti adhesive therapy and its companion diagnostic in sickle cell diseaseSCDSCDrelated complicationssuch as heart attack and strokecause considerable mortality and morbidity worldwideVaso occlusive crisisVOCthe hallmark of SCDis a recurrent painful episode that primarily drives patients to seek medical caresDespite the advances in pain managementa class of novel therapeutic agents that specific target on the underlying molecular mechanisms have shown a greater promise to effectively reduce the frequencyseverity and duration of these acute crisesand hopefully become the First in Class drugs for treating SCDAt the same timethe growing efforts in drug development also require the corresponding companion diagnostic test to better administrate a new therapy in individual patient with SCDUnfortunatelythese are no standardized clinical tools to monitor the status and disease and assess therapeutic outcomesFunctionallyour new hemoglobin modifiersPP compoundswork in a multi action model forprevention of hypoxia induced polymerization of hemoglobin Sincrease of hemoglobin affinity to oxygenandinhibition of the interaction between intra cellular hemoglobin and cell membranesThese effects are anticipated to not only lower the rate of VOCbut also ameliorate the overall SCD complicationsOn the other handthe proposed blood function assay utilizes microfluidic technologies to simulate in vivo microcirculation and evaluate pathological cell adhesion under physiological flow conditionsAs a resultthe testing is believed to be clinically relevantWe propose to use this microfluidic cell adhesion assay to evaluate therapeutic outcomes of hemoglobin modifiers on animal model to promote the understanding these investigational compounds for the future development in clinical trialsWe envision that our proposed work will eventually lead to the first personalized treatment to reduce the complications of SCD NARRATIVE Sickle Cell DiseaseSCDcauses significant morbidity and mortality and poses a significant public health burden in the USwith costs for healthcare services of exceeding $billion each yearCurrent management and treatment options are inadequate and suboptimaland there is no gold standard for clinical assessment of the diseaseTo address this urgent needa new anti sickling therapy and its companion diagnostic will be simultaneously developed in this SBIR