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. Public Health Relevance: 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.
Discl aim er: Please note that the following critiques were prepared by the reviewers prior to the Study Section meeting and are provided in an essentially unedited form. While there is opportunity for the reviewers to update or revise their written evaluation, based upon the group's discussion, there is no guarantee that individual critiques have been updated subsequent to the discussion at the meeting. Therefore, the critiques may not fully reflect the final opinions of the individual reviewers at the close of group discussion or the final majority opinion of the group. Thus the Resume and Summary of Discussion is the final word on what the reviewers actually considered critical at the meeting.
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| 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 |
