期刊
NEUROBIOLOGY OF DISEASE
卷 48, 期 2, 页码 255-270出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2012.05.005
关键词
Gene therapy; Viral vectors; Neuropathic pain; Nociceptive pain; Peripheral nervous system; Spinal cord; Animal models; Herpes simplex virus; Lentivirus; Retrovirus; Adenovirus; Adeno-associated virus; Plasmid DNA; Enkephalin; Endorphin; Glutamic acid decarboxylase; Interleukins; Neurotransmitters; Neurotrophins
资金
- NIDDK NIH HHS [P01 DK044935] Funding Source: Medline
- NINDS NIH HHS [R01 NS064988] Funding Source: Medline
Chronic pain is a major health concern affecting 80 million Americans at some time in their lives with significant associated morbidity and effects on individual quality of life. Chronic pain can result from a variety of inflammatory and nerve damaging events that include cancer, infectious diseases, autoimmune-related syndromes and surgery. Current pharmacotherapies have not provided an effective long-term solution as they are limited by drug tolerance and potential abuse. These concerns have led to the development and testing of gene therapy approaches to treat chronic pain. The potential efficacy of gene therapy for pain has been reported in numerous pre-clinical studies that demonstrate pain control at the level of the spinal cord. This promise has been recently supported by a Phase-I human trial in which a replication-defective herpes simplex virus (HSV) vector was used to deliver the human pre-proenkephalin (hPPE) gene, encoding the natural opioid peptides met- and leu-enkephalin (ENK), to cancer patients with intractable pain resulting from bone metastases (Fink et al., 2011). The study showed that the therapy was well tolerated and that patients receiving the higher doses of therapeutic vector experienced a substantial reduction in their overall pain scores for up to a month post vector injection. These exciting early clinical results await further patient testing to demonstrate treatment efficacy and will likely pave the way for other gene therapies to treat chronic pain. (C) 2012 Elsevier Inc. All rights reserved.
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