Tau Antibody-Conjugated, Photonic Nanoparticle-Based Theranostics for Alzheimer's Disease

PROJECT SUMMARY Alzheimerandapos s diseaseADis the most common form of dementiacharacterized by both senile plaques composed of AmyloidApeptide and neurofibrillary tanglesNFTscomposed of tau proteinBymillion Americans andmillion people globally are projected to develop ADWith the increasing incidence of AD and neurodegenerative tauopathiesthe need to develop reliable therapies to slow or prevent disease progression is criticalA drug that can halt the progression of AD would improve outcomes for millions of patientsThereforeInnoSense LLCISLand collaboratorthe University of Texas Medical BranchUTMBpropose to develop CyphonatolTMindocyanine photonanoparticle for tau oligomersan AD theranostic using selective tau oligomer antibodies conjugated on photonic nanoparticlespNPwhich are loaded with indocyanine greenICGand curcuminCurThese nanosizedandltnmpNP will be delivered intranasally and will penetrate the blood brain barrierBBBwithout any side effectRecentlyUTMB developed tau soluble oligomerToligantibodiesAbsTrabbit polyclonaland TOMAmouse monoclonaltargeting Toligboth showing significant correlation with AD severityWe will conjugate Tolig Ab on the surface of pNP using standard carbodiimide chemistryThis pNP will contain ICGa near infraredNIRimaging agentand Cura well known drug for pathogenic protein disaggregationICG and Cur are Food and Drug AdministrationFDAand Generally Recognized as SafeGRASapproved agentswhile the micelles will be formulated from biocompatiblecarboxyl functionalized polyethylene oxide polypropylene oxide polyethylene oxidePEO PPO PEOtriblock copolymersRecentlyNIR imaging has raised the importance of long wavelengthnmin illuminating tissueup tocentimetersThe ICG in Cyphonatol will illuminate the tau aggregate in the brain tissue for easy detection and monitoringIn Phase I ISL will validate a proof of concept of Cyphonatol pNP formulation for intranasal deliveryWe willformulate pNP to contain ICG and Curconjugate Tolig specific Abs on the surface of the pNP to form Cyphonatoldetermine the release kinetics and toxicity of Tolig in vitroestablish the feasibility of packaging Cyphonatol in an intranasal delivery device andestablish Cyphonatol bioavailability and bioefficacy in a working modelIn Phase IIwe willexpand our study with overexpressing human tau miceHtau and PL micein a larger cohort andestablish reproducibilitystabilitypharmacokineticsand bioefficacy within safe doseTeaming with the university and industrial partnersISL will build an efficient Tolig targeting drug to successfully reduce tau aggregationWe anticipate Cyphonatol will be safenon toxiceffectively disperse throughout the nasal cavity and reach the olfactory bulb mucosa nervesIt will penetrate the BBB to target tau aggregatesCyphonatol will improve AD outcomes by providing a therapy that will slow disease progress and or cure AD PROJECT NARRATIVE Bymillion Americans are projected to develop Alzheimerandapos s diseaseADyet there are currently no effective therapies or drug that can halt AD progressionIn this projectwe propose to use indocyanine greenNIR contrast agentand curcumin encapsulated in PluronicFto develop tau soluble oligomer antibody conjugated photonic nanoparticleCyphonatolfor AD theranosticsCyphonatol will be used to monitor disease progress with live imaging and slow or cure AD