title: An Engineered Endomorphin-2 Gene for Morphine Withdrawal Syndrome.
abstract: An optimal therapeutics to manage opioid withdrawal syndrome is desired for opioid addiction treatment. Down-regulation of endogenous endomorphin-2 (EM2) level in the central nervous system after continuous morphine exposure was observed, which suggested that increase of EM2 could be an alternative novel method for opioid dependence. As a short peptide, the short half-life of EM2 limits its clinical usage through conventional administration. In the present study, we engineered an EM2 gene using a signal peptide of mouse growth factor for an out-secretory expression of EM2 and an adenovirus as a vector, which ultimately sustained the release of EM-2. After administration of the adenovirus in central nervous system, a sustained increase of EM2 level in the cerebral spinal fluid (CSF) was observed along with a reduction of morphine withdrawal syndrome. These findings suggest that the engineered EM2 gene delivered to the central nervous system could be a novel therapeutics for withdrawal syndrome in opioid dependent subjects.
authors.affiliation: Department of Anesthesiology & Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.|Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, United States of America.
authors.forename: Fei-Xiang
authors.initials: FX
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Dongfang Hospital, Fujian, 354200, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Anesthesiology & Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.
authors.forename: Hui-Ting
authors.initials: HT
authors.lastname: Di
authors.affiliation: Department of Anesthesiology & Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology & Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.
authors.forename: Rui-Rui
authors.initials: RR
authors.lastname: Pan
authors.affiliation: Department of Anesthesiology & Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, United States of America.
authors.forename: Renyu
authors.initials: R
authors.lastname: Liu
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002555:Cerebrospinal Fluid / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D008297:Male; D051379:Mice; D009020:Morphine / Q000009:adverse effects* / Q000378:metabolism; D009842:Oligopeptides / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105294:endomorphin 2; D009020:Morphine