Preclinical Development of an NT3-expressing HSV Vector

描述(由申请人提供)：预防神经病的有效治疗方法的发展一直令人失望地缓慢，部分原因是很难将神经营养多肽输送到目标组织。为了克服这一局限性，我们构建了一系列基于单纯疱疹病毒(HSV)的非复制型载体，通过皮肤接种将基因有效地靶向背根节，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原的非复制型单纯疱疹病毒载体用于癌症顽固性疼痛患者的1期临床试验。对于化疗引起的周围神经病变的有效治疗存在大量未得到满足的需求，这限制了癌症化疗，我们的临床前动物研究证明，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，以获得表达NT3的HSV载体的IND和IRB批准，以便在将接受顺铂治疗的癌症患者中继续进行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.