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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01NS069378-02
Application #
8326048
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Gwinn, Katrina
Project Start
2011-09-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$1,056,121
Indirect Cost
$369,294
Name
University of Michigan Ann Arbor
Department
Neurology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Simonato, Michele; Bennett, Jean; Boulis, Nicholas M et al. (2013) Progress in gene therapy for neurological disorders. Nat Rev Neurol 9:277-91