Development of an ophthalmic diagnostic probe for cerebral amyloid angiopathy in patients

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Project Summary Cerebral amyloid angiopathy (CAA) is a common neuropathological finding among older adults and is characterized by amyloid beta (Aβ) deposits in blood vessel walls of the brain. CAA is a major cause of spontaneous intracerebral hemorrhage and is an important contributor to age related cognitive decline. Diagnosis is often missed by physicians as the presenting symptoms are similar to a stroke and can be further complicated as CAA is found in over 80% of Alzheimer's disease patients. Standard diagnosis of probable CAA involves expensive imaging techniques and an invasive brain biopsy. The only definitive way to diagnose CAA is through post-mortem analysis. An antemortem diagnostic is needed that can reliably identify CAA at the early, asymptomatic stages, enabling a correct diagnosis to avoid medications contraindicated in the disease, which can increase the individual's stroke risk. Furthermore, a useful and affordable outcome marker is needed for clinical trials focused on therapies for CAA that could stop or reverse the progression of the disease. Amydis aims to address these unmet needs by identifying A in the eye, as a window to the brain, for early detection of CAA. Amydis is meeting this need with the development of a novel retinal diagnostic probe. Our novel retinal diagnostic probe, AMDX-2011P, has fluorescent properties amenable for use with standard retinal imaging equipment found in the ophthalmologists' office and fluoresces at a wavelength suitable for use with conventional instruments, it penetrates the retina when administered systemically at significant concentrations, is non-toxic in preclinical animal models, and has crystalline properties that allow for consistent large-scale manufacturing. In this proposal, Amydis will manufacture AMDX-2011P under GMP guidelines, formulate AMDX-2011P for i.v. delivery, test stability, and then undertake a phase 1 clinical trial with single ascending doses in healthy subjects (N=24) and then test the optimal dose in a small cohort of CAA patients (N=5). Completion of these aims will advance the development of our in vivo ocular diagnostic test, getting us one step closer to our mission of providing an antemortem, simple, and affordable CAA diagnostic.