Regulatable Gene Expression for Prevention of Neuropathy

用于预防神经病变的可调节基因表达

• 批准号: 8540668
• 负责人: DAVID J. FINK
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8540668
• 关键词: Address; Animal Model; Animals; Antineoplastic Agents; Behavior; Cisplatin; Clinic; Clinical; Clinical Treatment; Clinical Trials; Development; Diabetes Mellitus; Diabetic Neuropathies; Dose; Dose-Limiting; Doxycycline; Erythropoietin; FDA approved; Gene Expression; Gene Transfer; HSV vector; Interleukin-10; Intervention; Intractable Pain; Kinetics; Malignant Neoplasms; Modeling; Morphology; Nerve; Nerve Fibers; Neurons; Neuropathy; Neurotrophin 3; Paclitaxel; Pain; Patients; Peptides; Peripheral Nervous System; Peripheral Nervous System Diseases; Pharmaceutical Preparations; Phase II Clinical Trials; Physicians; Prevention; Quality of life; Rattus; Rodent Model; Simplexvirus; Spinal Ganglia; Testing; Tetanus Helper Peptide; Time; Toxic effect; Translating; Veterans; Work; abstracting; base; chemotherapy; clinical application; clinically relevant; density; design; diabetic; disability; expression vector; mouse model; neurotrophic factor; pain behavior; preclinical study; preproenkephalin; prevent; protective effect; public health relevance; response; sciatic nerve; symptom management; transgene expression; vector; vector-induced

DESCRIPTION (provided by applicant): PROJECT SUMMARY/ABSTRACT 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.

描述（由申请人提供）：