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A human trial of HSV-mediated gene transfer for the treatment of chronic pain

Gene Therapy volume 16, pages 455–460 (2009)Cite this article

Abstract

Gene transfer to the dorsal root ganglion using replication defective herpes simplex virus (HSV)-based vectors reduces pain-related behaviors in rodent models having inflammatory pain, neuropathic pain and pain caused by cancer in bone. HSV vectors engineered to produce inhibitory neurotransmitters, including the delta opioid agonist peptide enkephalin, the mu opioid agonist peptide endomorphin-2 and glutamic acid decarboxylase (GAD), to effect the release of gamma amino butyric acid (GABA) act to inhibit nociceptive neurotransmission at the first synapse between primary nociceptive and second-order neuron in the dorsal horn of the spinal cord. HSV vectors engineered to release anti-inflammatory peptides, including interleukin (IL)-4, IL-10 and the p55 soluble tumor necrosis factor α (TNFα) receptor reduce neuroimmune activation in the spinal dorsal horn. The path leading from preclinical animal studies to the ongoing phase 1 human trial of the enkephalin-producing vector in patients with pain from cancer, and plans for an efficacy trial with an opioid-producing vector in inflammatory pain and an efficacy trial with a GAD-producing vector in diabetic neuropathic pain are outlined.

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Acknowledgements

We acknowledge the substantial contributions of many collaborators in the work reviewed including: Joseph Glorioso, Bill Goins and James Goss (University of Pittsburgh), Jim Wechuck and David Krisky (Diamyd Incorporated), Shuanglin Hao, Munmun Chattopadhyay, Zhigang Zhou and Xiangmin Peng (University of Michigan) and Jun Liu (deceased). This work was supported by NIH grants NS044507, NS038850, DK044935, grants from the Department of Veterans Affairs and the Juvenile Diabetes Research Foundation. Darren Wolfe is an employee of Diamyd Incorporated, a wholly owned subsidiary of Diamyd Medical, which is sponsoring the human trial of HSV-mediated gene transfer for pain. David Fink receives research funding from Diamyd in support of that trial; he has no equity interest in or other financial relationship with Diamyd. Dr Mata has no conflict of interest to declare.

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Authors and Affiliations

  1. Diamyd Inc., Pittsburgh, PA, USA

    D Wolfe

  2. Department of Neurology, University of Michigan and Neurology Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA

    M Mata & D J Fink

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  1. D Wolfe
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  2. M Mata
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Correspondence to D J Fink.

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Wolfe, D., Mata, M. & Fink, D. A human trial of HSV-mediated gene transfer for the treatment of chronic pain. Gene Ther 16, 455–460 (2009). https://doi.org/10.1038/gt.2009.17

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