Preclinical Development of an NT3-expressing HSV Vector

描述（由申请人提供）：令人失望的是，预防神经病变的有效治疗方法的发展缓慢，部分原因是难以将神经营养肽输送到目标组织。为了克服这一限制，我们构建了一系列基于非复制性单纯疱疹病毒（HSV）的载体，这些载体通过皮肤接种有效地靶向基因传递到背根神经节，从而影响转导神经元释放神经保护肽。我们已经将一种表达前脑啡肽的非复制性HSV载体带入了一期临床试验，用于治疗癌症引起的难治性疼痛。对化疗诱导的周围神经病变的有效治疗存在大量未满足的需求，这限制了癌症化疗，我们的临床前动物研究表明，表达神经营养因子-3 （NT3）的HSV载体在顺铂神经病变的啮齿动物模型中是有效的。因此，我们寻求资金来完成临床前步骤，以获得IND和IRB批准表达nt3的HSV载体，以便在接受顺铂治疗的癌症患者中进行1/2期临床试验。

DESCRIPTION (provided by applicant): The development of effective treatments to prevent neuropathy has been disappointingly slow, in part because it is difficult to deliver neurotrophic peptides to the target tissue. To overcome this limitation we have constructed a series of non-replicating herpes simplex virus (HSV)-based vectors that efficiently target gene delivery to dorsal root ganglia from skin inoculation to effect release of neuroprotective peptides from transduced neurons. We have already taken a non-replicating HSV vector expressing preproenkephalin into phase 1 clinical trial in patients with intractable pain from cancer. There is a substantial unmet need for effective treatments chemotherapy-induced peripheral neuropathy that limits cancer chemotherapy, and we have preclinical animal studies to demonstrate that a neurotrophin-3 (NT3)-expressing HSV vector is effective in the rodent model of cisplatin neuropathy. Therefore we seek funding to complete the preclinical steps required to obtain IND and IRB approval of an NT3-expressing HSV vector in order to proceed with a phase 1/2 clinical trial in patients with cancer who will receive cisplatin treatment.