title: Gene therapy for pain: results of a phase I clinical trial.
abstract: OBJECTIVE
  Preclinical evidence indicates that gene transfer to the dorsal root ganglion using replication-defective herpes simplex virus (HSV)-based vectors can reduce pain-related behavior in animal models of pain. This clinical trial was carried out to assess the safety and explore the potential efficacy of this approach in humans.
  
  
  METHODS
  We conducted a multicenter, dose-escalation, phase I clinical trial of NP2, a replication-defective HSV-based vector expressing human preproenkephalin (PENK) in subjects with intractable focal pain caused by cancer. NP2 was injected intradermally into the dermatome(s) corresponding to the radicular distribution of pain. The primary outcome was safety. As secondary measures, efficacy of pain relief was assessed using a numeric rating scale (NRS), the Short Form McGill Pain Questionnaire (SF-MPQ), and concurrent opiate usage.
  
  
  RESULTS
  Ten subjects with moderate to severe intractable pain despite treatment with >200mg/day of morphine (or equivalent) were enrolled into the study. Treatment was well tolerated with no study agent-related serious adverse events observed at any point in the study. Subjects receiving the low dose of NP2 reported no substantive change in pain. Subjects in the middle- and high-dose cohorts reported pain relief as assessed by NRS and SF-MPQ.
  
  
  CONCLUSIONS
  Treatment of intractable pain with NP2 was well tolerated. There were no placebo controls in this relatively small study, but the dose-responsive analgesic effects suggest that NP2 may be effective in reducing pain and warrants further clinical investigation.
authors.affiliation: Department of Neurology, University of Michigan and VA Ann Arbor Healthcare System, Ann Arbor, MI, USA. djfink@umich.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Fink
authors.forename: James
authors.initials: J
authors.lastname: Wechuck
authors.forename: Marina
authors.initials: M
authors.lastname: Mata
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Glorioso
authors.forename: James
authors.initials: J
authors.lastname: Goss
authors.forename: David
authors.initials: D
authors.lastname: Krisky
authors.forename: Darren
authors.initials: D
authors.lastname: Wolfe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use; D015337:Multicenter Studies as Topic; D009369:Neoplasms / Q000503:physiopathology; D059408:Pain Management; D010147:Pain Measurement; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use*; D011795:Surveys and Questionnaires
chemical_list: D000701:Analgesics, Opioid; D004745:Enkephalins; D011498:Protein Precursors; D009020:Morphine; C033660:preproenkephalin