Magazine article Clinical Psychiatry News

Gene Therapy Showing Early Promise for Chronic Pain

Magazine article Clinical Psychiatry News

Gene Therapy Showing Early Promise for Chronic Pain

Article excerpt


BETHESDA, MD. - Gene therapy is showing promise in early trials as a novel targeted approach to alleviating chronic pain while avoiding the off-target side effects common to most oral analgesics.

The genetic therapy approach is potentially appropriate for patients with focal musculoskeletal pain.

"We are only just now starting the phase II trial, but in principle the approach could be applied to intractable joint pain in a patient in whom joint replacement is not an option," Dr. David J. Fink said in an interview.

However, gene therapy would not be applicable to a problem of diffuse multifocal pain such as that seen in patients fibromyalgia, Dr. Fink added.

Clinical research, funded by Diamyd Inc., is now entering phase II human trials, said Dr. Fink, who is the Robert Brear Professor and chair of the department of neurology at the University of Michigan, Ann Arbor.

The use of most standard oral analgesics to treat long-term chronic pain is severely limited because of their effects on neural pathways unrelated to the pain or on organs outside the nervous system, leading to side effects such as lethargy, confusion, and respiratory suppression.

And, in the case of opiates, there is the added potential for addiction and abuse.

To overcome this problem, Dr. Fink and his associates have constructed a series of nonreplicating herpes simplex virus-based vectors that target gene delivery to the dorsal root ganglion via skin inoculation.

Herpes simplex was chosen as a vector because it is a naturally neurotropic virus, he said.

In preclinical research supported by the National Institutes of Health and the Department of Veterans Affairs, Dr. Fink and his colleagues demonstrated that an HSV vector that produces the opioid peptide enkephalin reduces pain-related behavior in animal models of inflammatory pain, neuropathic pain, and pain caused by cancer (Pain Medicine 2009;10:1325-30).

A phase I human trial of a human-grade nonreplicating HSV vector expressing preproenkephalin has now been completed.

Safety was the primary outcome, with secondary outcomes including evaluation of pain and performance status using the numeric rating scale (NRS) for evaluation of pain, along with other measures of pain and general health and function and concurrent analgesic drug use.

No serious vector-related adverse events were observed in the study, which enrolled 10 patients who had intractable localized cancer pain rated greater than 4 of 10 on a visual analog scale, despite taking at least 200 mg/day of oral morphine or the equivalent. …

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