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. INTERPRETATION: 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.
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 humanpreproenkephalin (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. INTERPRETATION: 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: Munmun Chattopadhyay; Darren Wolfe; Shaohua Huang; James Goss; Joseph C Glorioso; Marina Mata; David J Fink Journal: Ann Neurol Date: 2002-01 Impact factor: 10.422
Authors: N Cherny; C Ripamonti; J Pereira; C Davis; M Fallon; H McQuay; S Mercadante; G Pasternak; V Ventafridda Journal: J Clin Oncol Date: 2001-05-01 Impact factor: 44.544
Authors: James R Goss; Cara F Harley; Marina Mata; Mark E O'Malley; William F Goins; XiaoPing Hu; Joseph C Glorioso; David J Fink Journal: Ann Neurol Date: 2002-11 Impact factor: 10.422
Authors: Gerardo Casanova; Rosalia Cancela; Lourdes Alonzo; Rosa Benuto; Maria del Carmen Magana; Dennis R Hurley; Eugenia Fishbein; Claudia Lara; Teresa Gonzalez; Rebeca Ponce; Joseph W Burnett; Gary J Calton Journal: Cutis Date: 2002-10
Authors: J M Markert; M D Medlock; S D Rabkin; G Y Gillespie; T Todo; W D Hunter; C A Palmer; F Feigenbaum; C Tornatore; F Tufaro; R L Martuza Journal: Gene Ther Date: 2000-05 Impact factor: 5.250
Authors: V Papanastassiou; R Rampling; M Fraser; R Petty; D Hadley; J Nicoll; J Harland; R Mabbs; M Brown Journal: Gene Ther Date: 2002-03 Impact factor: 5.250
Authors: Michele Simonato; Jean Bennett; Nicholas M Boulis; Maria G Castro; David J Fink; William F Goins; Steven J Gray; Pedro R Lowenstein; Luk H Vandenberghe; Thomas J Wilson; John H Wolfe; Joseph C Glorioso Journal: Nat Rev Neurol Date: 2013-04-23 Impact factor: 42.937