Chemotherapy-induced peripheral neuropathy (CIPN) is the dose-limiting toxicity for many commonly utilized classes of anti-cancer agents, and there are no currently available FDA-approved interventions to prevent CIPN. In animal models CIPN can be prevented by systemic administration of neurotrophic factors, but translating these findings into a clinical treatment has been limited by off-target effects that preclude systemic administration. Over the past decade we have addressed this issue by gene transfer using vectors created from replication incompetent herpes simplex virus (HSV) to achieve local release of peptides from dorsal root ganglion (DRG) neurons, and our HSV vector expressing preproenkephalin is now in a phase 2 clinical trial for treatment of intractable pain. To safely express neurotrophic factors n the peripheral nervous system for a condition that extends over a prolonged timeframe, it will be essential to be able to regulate transgene expression. Studies proposed in this application are designed to extend our previous work to determine whether regulated expression of either neurotrophin-3 (NT3) and/or interleukin-10 (IL10) from non-replicating HSV vectors can be used to prevent CIPN.
Chemotherapy-induced peripheral neuropathy (CIPN) is the dose-limiting toxicity for many classes of anti- cancer agents commonly used to treat veterans, and there are no currently available FDA-approved interventions to prevent CIPN. To safely express neurotrophic factors in the peripheral nervous system for a condition that extends over a prolonged timeframe, it will be essential to be able to regulate transgene expression. Studies proposed in this application are designed to extend our previous work to determine whether regulated expression of either neurotrophin-3 (NT3) and/or interleukin-10 (IL10) from non-replicating HSV vectors can be used to prevent CIPN.
| Kawata, Daisuke; Wu, Zetang (2017) Rgulatable Transgene Expression for Prevention of Chemotherapy-Induced Peripheral Neuropathy. Mol Ther Methods Clin Dev 6:91-101 |
| Kawata, Daisuke; Wu, Zetang (2017) Regulatable Transgene Expression for Prevention of Chemotherapy-Induced Peripheral Neuropathy. Mol Ther Methods Clin Dev 6:91-101 |
| Wu, Z; Wang, S; Wu, I et al. (2015) Activation of TLR-4 to produce tumour necrosis factor-? in neuropathic pain caused by paclitaxel. Eur J Pain 19:889-98 |
