University of Michigan
Ann Arbor VA Healthcare System
Ann Arbor, Michigan
The treatment of pain with pharmacologic agents is often limited by dose-dependent side effects that develop when drugs are delivered systemically. Gene therapy offers an avenue to provide continuous and targeted production of analgesic neurotransmitters, resulting in higher effective concentrations of the therapeutic agent in the affected area of the peripheral nervous system. Based on data from preclinical studies, dorsal root ganglion synapses of primary sensory neurons were targeted by inoculating skin with a vector engineered from herpes simplex virus (HSV) type 1. This paper describes the rationale behind and design of the first human trial of gene therapy for chronic pain—a Phase I study examining the safety of an HSV-based vector engineered to transiently express preproenkephalin in patients with intractable cancer pain. Other trials will employ a similar approach to examine alternative inhibitory neurotransmitters in the treatment of diabetic peripheral neuropathic pain.
A Clinical Trial of Gene Therapy for Chronic Pain
David J. Fink, MD
University of Michigan
Ann Arbor VA Healthcare System
Ann Arbor, Michigan
The treatment of pain with pharmacologic agents is often limited by dose-dependent side effects that develop when drugs are delivered systemically. Gene therapy offers an avenue to provide continuous and targeted production of analgesic neurotransmitters, resulting in higher effective concentrations of the therapeutic agent in the affected area of the peripheral nervous system. Based on data from preclinical studies, dorsal root ganglion synapses of primary sensory neurons were targeted by inoculating skin with a vector engineered from herpes simplex virus (HSV) type 1. This paper describes the rationale behind and design of the first human trial of gene therapy for chronic pain—a Phase I study examining the safety of an HSV-based vector engineered to transiently express preproenkephalin in patients with intractable cancer pain. Other trials will employ a similar approach to examine alternative inhibitory neurotransmitters in the treatment of diabetic peripheral neuropathic pain.
References
1. Wolfe D, Wechuck J, Krisky D, Mata M, Fink DJ. A clinical trial of gene therapy for chronic pain. Pain Med. 2009;10(7):1325-1330.
2. Mata M, Hao S, Fink DJ. Applications of gene therapy to the treatment of chronic pain. Curr Gene Ther. 2008;8:42-48.
3. Goss JR, Harley CF, Mata M, et al. Herpes vector-mediated expression of proenkephalin reduces pain-related behavior in a model of bone cancer pain. Ann Neurol. 2002;52:662-665.