VEGF gene transfer for diabetic neuropathy

Area of Science:

• Neurology
• Genetics
• Vascular Biology

Background:

• Diabetic peripheral neuropathy is a common complication leading to significant morbidity, including foot ulceration and amputation.
• Microvascular disruption in peripheral nerves is implicated as a cause of diabetic neuropathy.
• Previous studies suggest potential benefits of vascular endothelial growth factor (VEGF) in treating neuropathy associated with vascular occlusive disease.

Purpose of the Study:

• To evaluate the safety and impact of phVEGF165 gene transfer on sensory neuropathy in diabetic patients.
• To assess efficacy in patients with and without macrovascular disease in the lower extremities.
• To explore VEGF gene transfer as a novel treatment strategy for diabetic neuropathy.

Main Methods:

• Phase I/II, single-site, dose-escalating, double-blind, placebo-controlled study.
• 192 diabetic patients (>21 years) with sensory neuropathy will be recruited over 4 years.
• Patients randomized (3:1) to receive escalating doses of phVEGF165 (1, 2, or 4 mg) or placebo, administered via intramuscular injections.

Main Results:

• Animal models showed that VEGF gene transfer restored nerve vascularity and blood flow, reversing neuropathy.
• Constitutive VEGF overexpression led to the restoration of both large and small fiber peripheral nerve function in diabetic models.
• This study aims to translate these findings to human subjects, evaluating safety and impact in diabetic patients.

Conclusions:

• Microvascular disruption is a key factor in diabetic neuropathy.
• Angiogenic growth factors, such as VEGF, show promise as a novel therapeutic approach.
• Further clinical investigation is warranted to confirm safety and efficacy in human subjects.