Problem

Peripheral neuropathy (PN) results in loss of innervation by the peripheral nerves in tissues such as skin, muscle, heart and subcutaneous white adipose tissue (scWAT). It is mostly associated with diabetes, obesity, aging, and chemotherapy. Affecting 10-20% of U.S. adults aged 50-70, PN is a chronic, painful, debilitating disease, burdened by high healthcare costs. Despite its prevalence and impact, current therapies focus solely on pain management and fail to restore nerve function or regeneration within tissues. There is a dire need for solutions that go beyond symptom control and improve outcomes.

Solution

• Researchers at OSU have developed an adeno-associated virus (AAV) platform using the Rec2 serotype, which exhibits strong tropism for adipocytes, to deliver either brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF) directly into tissues. By targeting adipocytes to release neurotrophic factors, the therapy aims to stimulate axon outgrowth and improve tissue-specific small fiber innervation
• AAVRec2-BDNF intra-adipose delivery increased axon outgrowth and improved tissue innervation in genetic and diet-induced mouse models of diabetic peripheral neuropathy (DPN), albeit the reduced efficacy after longer periods of dietary obesity suggests a critical therapeutic window. AAVRec2-NGF increased scWAT innervation in obese mice more effectively than BDNF, even after 25 weeks of dietary obesity, likely because adipocytes are an endogenous source of NGF
• The team demonstrated that their theragnostic device DEN-TEN (Detecting Early Neuropathy to Treat Peripheral Neuropathy) can effectively deliver AAV-based gene therapy fluids to the subcutaneous adipose tissue through a microneedle array with pump delivery, which results in increased tissue innervation

Applications

• Treatment of small fiber peripheral neuropathy and/or adipose neuropathy, including due to diabetes/obesity, alone or in combination with existing therapies
• Potential use to treat aging-related PN, chemotherapy-induced PN, and other tissues (muscle, liver, CNS) with neuropathic degeneration

Advantages

• Targeted delivery to adipocytes ensures sustained local expression of neurotrophic factors while minimizing off-target effects, such as transduction in the CNS
• AAVs are an FDA-approved platform with low immunogenicity
• The DEN-TEN device enables diffuse, minimally invasive administration across a broad tissue region, or targeting subdermal adipose depots, and represents a significant advancement over systemic delivery, which has historically been limited by poor tissue penetration and side effects
• This innovative technology addresses the root cause of peripheral neuropathy (nerve degeneration) rather than managing the symptoms

Seeking opportunities for co-development or out-licensing