HSV vectors for gene therapy of chronic pain.
Chronic pain is a serious debilitating condition affecting a large number of individuals and with substantial societal impact in terms of quality-of-life and absence from work. Current therapies often exhibit activity at sites other than the nervous system and so are limited by 'off-target' adverse effects. These adverse effects often prevent the administration of an effective therapeutic dose of the approved drug(s). Viral vectors have the potential to deliver and express short-lived, but potent therapeutic peptides in the nervous system. Vector-expressed peptides interrupt or modulate the transmission of nociceptive signals without systemic distribution or off-target effects. This review focuses on the use of non-replicating HSV-based vectors that are introduced into the skin and transduce dorsal root ganglia to express analgesic molecules locally in the spinal cord. Data from preclinical animal models as well as studies that support early phase clinical trials from 2002 to 2008 are described.
Srinivasan
Rahul
R
University of Pittsburgh School of Medicine, Department of Molecular Genetics and Biochemistry, Pittsburgh, PA 15261, USA.
Fink
David J
DJ
Glorioso
Joseph C
JC
D000698:Analgesia; D000700:Analgesics; D002908:Chronic Disease; D005727:Ganglia, Spinal / Q000378:metabolism; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D010146:Pain / Q000235:genetics; D059408:Pain Management; D018139:Simplexvirus / Q000235:genetics; D013001:Somatoform Disorders / Q000235:genetics / Q000628:therapy*; D013131:Spine / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods
D000700:Analgesics