Gene Therapy

Gene Therapy

PEP Topic 
Chronic Pain

Gene therapy was examined for its effect on pain in patients with cancer. A gene transfer vector was injected intradermally into dermatomes corresponding to the individual’s pain distribution in a phase I trial.

Effectiveness Not Established

Research Evidence Summaries

Fink, D.J., Wechuck, J., Mata, M., Glorioso, J.C., Goss, J., Krisky, D., & Wolfe, D. (2011). Gene therapy for pain: Results of a phase I clinical trial. Annals of Neurology, 70, 207–212.

doi: 10.1002/ana.22446

Study Purpose:

To assess the safety of the herpes simplex virus (HSV)–based gene transfer platform (dose escalation)

To evaluate the delivery of vector-mediated delivery of PENK on pain and on concurrent use of opioid medication

Intervention Characteristics/Basic Study Process:

NP2, an HSV vector, was injected intradermally into the dermatome(s) corresponding to the radicular pattern of pain: Pain relief was a secondary measure evaluated by a numeric rating scale (NRS) and the Short Form McGill Pain Questionnaire (SF-MPQ) on day 0 prior to doing and on postdosing days 1, 3, 7, 10, 14, 21, and 28. An SF-12 Short-Form Health Survey and complete Eastern Cooperative Oncology Group (ECOG) performance status were also completed on days 0 and 28. Concurrent opiate analgesic use was recorded on postdosing days 1, 3, 7, 10, 14, 21, and 28. Phase I dose escalation was administered as 10 intradermal injections of approximately 100 microliters (total 1.0 ml) distributed within the dermatome corresponding to the radicular distribution of the pain in a single session on study day 0. The first cohort (four patients) was given a dose of 1 x 10^7 plaque-forming units (pfu) and monitored for four weeks. A second cohort (three patients) was given 1 x 10^8 pfu, and a third cohort (three patients) was given 1 x 10^9 pfu. Patients were observed for at least 12 hours after dosing before being discharged and were scheduled for reexamination at 1, 3, 7, 10, 14, 21, and 28 days postdosing and monthly thereafter. The primary outcome was safety, so patients received a full evaluation for adverse events, physical examination, vital signs, mucositis evaluation, and labs.

Sample Characteristics:

  • The study reported on 10 patients.
  • Mean patient age was 63.3 years in cohort 1, 51.3 years in cohort 2, and 73 years in cohort 3.
  • The sample was 70% female and 30% male.
  • Patients had primary or metastatic cancer and were experiencing moderate-to-severe intractable pain despite doses of more than 200 mg of morphine or equivalents.


  • Multisite
  • Outpatient setting
  • University of Michigan

Phase of Care and Clinical Applications:

  • Patients were receiving end-of-life care.
  • The study has clinical applicability for end-of-life and palliative care.

Study Design:

The study was a phase I trial.

Measurement Instruments/Methods:

  • NRS (0–10) pain scale at one-week intervals for 28 days    
  • SF-MPQ at one-week intervals for 28 days
  • Concurrent opioid usage
  • SF-12 Health Survey
  • ECOG performance


Treatment was well-tolerated with no significant adverse effects attributable to the agent. The adverse events that were deemed as possibly related to treatment were all mild in severity and resolved. These included transient injection site erythema and pruritus, and one patient who had a transient elevation in body temperature. Those enrolled in the lowest dose of NP2 reported no changes in pain. Those enrolled in higher doses (cohorts 2 and 3) reported pain relief of approximately 50% on day 1 after dosing.


NP2 vector appears to be safe, and the method has potential to improve intractable pain. Pain relief was difficult to interpret due to the small number of patients and no control group.


  • The study had a small sample size, with less than 30 patients.
  • No placebo group was used for comparison.

Nursing Implications:

Further investigation of this novel treatment is needed.