The body naturally manufactures many of its own natural molecules for back pain management. Endorphins and enkephalins interact with opioid receptors to reduce the body’s perception of pain. Opioid pain relievers such as morphine mimic these natural molecules and stimulate their receptors in order to block pain. However, with time, the body becomes tolerant to the opioid pain medication and higher doses are needed. Prescription opiate treatments can have serious side effects such as sedation and respiratory depression, which limit their safety at high doses. As a result, opioids are not an ideal long term solution for chronic pain.
A new way to boost the body’s production of natural painkillers is by using viruses. Viruses are already ideally designed for getting into human cells, hijacking the cellular systems that make proteins, and then using these systems to make copies of themselves. Dr. David Fink’s laboratory at the University of Michigan reprogrammed a virus so that instead of making the host cell produce copies of itself, it produces copies of the natural painkilling molecule enkephalin. When they tried the virus on mice with bone pain due to cancer, mice that received the drug had increased mobility compared to those who went untreated.1
This seemed promising, but to find out whether the virus really reduced pain, they needed to try it on a critter that could talk. They recruited 10 patients with intractable pain due to bone cancer. Patients that received the lowest dose of virus had no change in their pain, but those who received the medium and high doses had dramatic results. After one day, their pain was reduced to 50% of the pretreatment level, and after one week pain was reduced to 20%. Some subjects were even able to reduce their morphine doses as a result.2
Gene therapy is a powerful tool for treating diseases caused by deficiencies of biological molecules. The idea of gene therapy was first published in the journal Science in 19723 and the first United States FDA approved gene therapy study was conducted in 1990. The study supplied adenosine deaminase to deficient T cells, correcting the patients’ life threatening immunodeficiency.4 In 2012, the FDA approved Glybera as the first gene therapy treatment for correcting defective lipoprotein lipase in Familial Chylomicronemia Syndrome. As of this writing, a search for gene therapy studies on clinicaltrials.gov returns 3577 trials.
The collaboration between Dr Fink’s lab and Diamyd Incorporated has just finished enrolling patients for a multicenter Phase II double blind randomized controlled trial of their enkephalin gene treatment. They have also just finished mouse studies on a new treatment for incomplete spinal cord injury pain.5 The enzyme GAD is responsible for creating the inhibitory neurotransmitter GABA, which reduces pain after spinal cord injury. “Neuropathic pain is very difficult to control,” says Dr. David Fink, “By transferring the gene for GAD, we can substantially reduce this pain in rodents.” If the group can manage to navigate the maze to FDA approval, there will certainly be big payoffs at the end.
1. Goss, J. R. et al.Herpes vector-mediated expression of proenkephalin reduces bone cancer pain. Ann. Neurol.52, 662–665 (2002).
2. Fink, D. J. et al. Gene Therapy for Pain: Results of a Phase I Clinical Trial. Ann. Neurol.70, 207–212 (2011).
3. Friedmann, T. & Roblin, R. Gene therapy for human genetic disease? Science175, 949–955 (1972).
4. Blaese, R. M. et al. T Lymphocyte-Directed Gene Therapy for ADA− SCID: Initial Trial Results After 4 Years. Science270, 475–480 (1995).
5. Liu, J. et al. Peripherally Delivered Glutamic Acid Decarboxylase Gene Therapy for Spinal Cord Injury Pain. Mol. Ther.10, 57–66 (2004).