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.
With this application we are seeking funding to move forward with the preclinical development of an NT-3- expressing HSV vector for treatment of cancer patients who will receive cisplatin. Chemotherapy-induced peripheral neuropathy is a serious complication of therapy that substantially limits our ability to effectively treat patients with cancer, and for which there is currently no effective treatment.
| Wu, Zetang; Wang, Shiyong; Gruber, Sandy et al. (2013) Full-length membrane-bound tumor necrosis factor-? acts through tumor necrosis factor receptor 2 to modify phenotype of sensory neurons. Pain 154:1778-82 |
| Simonato, Michele; Bennett, Jean; Boulis, Nicholas M et al. (2013) Progress in gene therapy for neurological disorders. Nat Rev Neurol 9:277-91 |
| Wolfe, Darren; Mata, Marina; Fink, David J (2012) Targeted drug delivery to the peripheral nervous system using gene therapy. Neurosci Lett 527:85-9 |
