Imaging Probes for Precision Medicine in Alzheimer's Disease

Here I aim to develop and refine [18F]-labeled imaging tools to guide the clinical development of a new class of drugs with disease-modifying potential, the epichaperome targeting agents.

Matching the right patient to the right medicine is a goal of the future in medicine. In this proposal I aim to build tools that can be used to image and select those Alzheimer disease (AD) patients that are most likely to benefit from a new experimental medicine with disease-modifying potential. This medicine, PU-AD, developed by my laboratory, works by rebalancing cellular networks and brain circuits. In mouse models, it reverted cognitive dysfunction and is currently in clinical evaluation in AD and related disorders. Tools I develop here therefore have immediate translational potential.

The [18F]-labeled epichaperome probe could serve as a companion diagnostic to the therapeutic PU-AD or other emerging epichaperome therapies. The probe will complement this therapeutic platform – consisting of drug candidate, biomarker and diagnostic – with our ultimate goal being precision medicine for AD and ADRD. In addition, imaging epichaperomes may have clear diagnostic implications as the spatial distribution of brain network dysfunction via epichaperome imaging, could offer valuable information for tracking and staging within individuals and groups across the AD spectrum.

Application of imaging in human studies offers unique opportunities to understand pathophysiology and treatment. The epichaperome imaging probe may aid in determining the interaction of PU-AD with its target, in guiding initial dosing of epichaperome therapeutic agents, and in identifying patients most likely to benefit from epichaperome therapy. Importantly, this probe could be added to the currently available imaging biomarker portfolio for AD to capture the anticipated spatio-temporal progression of the disease from very early stage, facilitating early clinical intervention.