Cancer pain control possible with gene therapy

Mouse studies indicate successful pain relief, University of Pittsburgh researchers say

By “programming” a herpes simplex virus to deliver a gene-mediated pain-blocking protein at the cellular level, University of Pittsburgh researchers have been able to significantly reduce cancer-related pain in mice with tumors, the researchers report in the November issue of the journal Annals of Neurology. The paper, “Herpes vector-mediated expression of proenkephalin reduces bone cancer pain,” is now available online at the journal’s Web site, http://www.interscience.wiley.com/jpages/0364-5134/.

“Chronic pain is notoriously difficult to treat effectively,” said co-author Joseph Glorioso, Ph.D., chairman of the department of molecular genetics and biochemistry and director of the Molecular Medicine Institute at the University of Pittsburgh School of Medicine, and president of the American Society of Gene Therapy. “We’ve been able to show that using this virus can significantly reduce bone cancer pain – at least in mice.”

The investigators are pursuing necessary approvals to begin a clinical trial in patients with severe pain resulting from metastatic cancer, and hope to start enrolling patients sometime next year.

“We are excited about the possibility that this approach may help to control pain in patients who can’t get complete relief from the maximum current treatment,” said senior author David Fink, M.D., professor of neurology and molecular genetics and biochemistry at the University of Pittsburgh School of Medicine and chief of neurology and director of the Geriatric Research Education and Clinical Center at the Veterans Administration Pittsburgh Healthcare System.

Drs. Fink, Glorioso and their colleagues created an inactivated herpes simplex virus that carries the human gene for proenkaphalin, a naturally occurring painkilling peptide, a combination of amino acids.

Mice with tumors in a leg bone that received injections with the altered virus showed a substantial and significant reduction in pain-related behavior, the authors report.

“Although we have many powerful medications to treat pain, unwelcome side effects of these drugs limit our ability to relieve the most severe painful conditions,” said Dr. Fink. “Using the virus to deliver the natural painkilling peptide may help in those cases.”

These undesirable side effects can include excessive drowsiness, constipation and difficulty urinating.

“It remains to be seen how effective this may be in humans,” said Dr. Glorioso. “But what we have seen so far is encouraging.”

In addition to Drs. Fink and Glorioso, other authors include James Goss, Ph.D.; Marina Mata, M.D.; Cara Harley, B.S.; Xiaoping Hu and William Goins, Ph.D.

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