Poster abstracts
Poster number 102 submitted by Jake Willows
Targeting the peripheral nervous system in discrete tissues with AAV vectors
Jake W. Willows (The Ohio State University), Lindsey M. Lazor (The Ohio State University), Kristy L. Townsend (The Ohio State University)
Abstract:
Aging, obesity, and diabetes increase the risk of small fiber peripheral neuropathy (PN), a neurodegenerative disorder that affects tissues such as skin, muscle, and adipose. PN causes loss of innervation, disrupting neural communication and producing symptoms like numbness, tingling, burning, and pain. Despite impacting over 30 million Americans—including more than half of diabetic patients—no cure exists for neuropathy. As the US population ages and obesity and diabetes rates rise, understanding PN’s pathophysiology and developing novel treatments becomes increasingly urgent.
Adipose tissue is densely innervated by sensory and sympathetic nerves that regulate metabolic function through bidirectional brain communication. Subcutaneous white adipose tissue (scWAT) adapts to metabolic demands by remodeling its cellular structure, vascularization, and innervation. Disruption of this neural circuitry exacerbates metabolic dysfunction, making the discovery of “adipose neuropathy” significant for addressing metabolic diseases.
To develop gene therapy tools for targeting adipose nerves—and to advance neuropathy treatments building on prior work with adipocyte-tropic adeno-associated viruses (AAVs) delivering neurotrophic factors—we sought specific and effective AAV serotypes for peripheral nerve targeting. Unlike the brain, where many AAVs efficiently transduce neurons, targeting peripheral nerves may require tissue-specific approaches. We compared various AAV serotypes by assessing transgene expression in scWAT and the dorsal root ganglia (DRG) housing sensory neurons. Immunostaining for calcitonin gene-related peptide (CGRP) confirmed successful transduction of peptidergic sensory fibers in Nav1.8-Cre::ZsGreen1 reporter mice. We further optimized transduction by evaluating promoter sequences, delivery routes, and viral titers. Our findings demonstrate proof-of-concept for chemogenetic (DREADD) stimulation of adipose nerves, laying the groundwork for studies to promote neural regeneration and counteract neuropathy. Enhancing reinnervation holds promise for transformative treatments for metabolic diseases linked to neuropathy.
Keywords: Adipose, Peripheral Nervous System