Development of an ophthalmic diagnostic probe for neurodegenerativedisorders

Project Summary Deposition of amyloid plaques in the brain represents a universal feature Alzheimer s disease pathology and precedes clinical symptoms by several years Currently diagnosis of amyloid associated dementias in individuals showing symptoms of cognitive decline is extremely difficult requiring multiple modes of testing over months to years Early pre symptomatic diagnosis is even more challenging if not impossible with currently available technology A non invasive method for diagnosing Alzheimer s disease is greatly needed We will further evaluate the use of AMDX a novel fluorescent probe that can label amyloids in tissue as a diagnostic for Alzheimer s disease AMDX has been shown to fluorescently label AD related deposits in vivo Importantly this probe has also been shown to effectively image amyloid deposits in the retina of AD mice following both topical and intravenous dosing The properties of AMDX are ideal for its development as a topical diagnostic probe for AD The studies outlined in this proposal advance AMDX to the Pre IND stage The synthesis of AMDX will be optimized through dedicated process development activities A formulation effective for topical administration in humans will be developed along with in vivo evaluation of diagnostic efficacy in two species of animals Further the retinal images obtained throughout formulation development will be utilized to develop a method to quantify the number size and intensity of amyloid deposits Together the aims of this proposal will result in an optimized diagnostic product capable of imaging AD in the retina The diagnostic product will be advanced to the point of being ready for IND enabling Toxicology studies Project Narrative Alzheimer s disease is characterized by the deposition of insoluble protein aggregates in the brain that are referred to as amyloids Recently these amyloids have been identified in retinal tissue in diseased individuals The proposed research aims advance a topical diagnostic to image amyloid deposits