Gene Therapy Offers New Hope For Treatment Of Peripheral Neuropathy

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Gene Therapy Offers New Hope For Treatment Of Peripheral Neuropathy

http://www.medicalnewstoday.com/medicalnews.php?newsid=72790

Researchers from the University of Pittsburgh School of Medicine

report that they have successfully used gene therapy to block the

pain response in an animal model of neuropathic pain, a type of

chronic pain in people for which there are few effective treatments.

These findings were presented at the 10th annual meeting of the

American Society of Gene Therapy.

Neuropathic pain is the result of damage to nerve fibers caused by

injuries or diseases, such as diabetes and cancer. These damaged

nerve fibers continue to send signals to pain centers in the brain

even after the surrounding tissue has healed. Unfortunately,

neuropathic pain often responds poorly to standard pain treatments

and occasionally may get worse instead of better over time. For some

people, it leads to serious, long-term disability and dependence on

pain medications that have a variety of unwanted side effects,

including addiction.

The Pitt research team, led by ph Glorioso, III, Ph.D., chair of

the department of biochemistry and molecular genetics, University of

Pittsburgh School of Medicine, used a genetically engineered herpes

simplex virus (HSV) to deliver the gene for part of the human

glycine receptor (GlyR), a receptor found primarily on the surface

of nerve cells in the spinal cord and the lower brain but not in the

nerves in the limbs, to the paws of rats. A group of control rats

received only the HSV vector without the inserted gene. After the

delivery of the therapeutic gene or empty vector (for the control

group), the researchers injected the same paws of each rat with

formalin, an irritant known to simulate the symptoms of a peripheral

neuropathic pain at the site of injection. Following formalin

injection, the rats were then given an injection of glycine to

activate the GlyR receptor.

Both control and GlyR-HSV-infected rats showed a typical pain

response to formalin. However, the application of glycine eliminated

the pain response in GlyR-HSV infected animals, while it had no

effect on animals infected with vector only. This alleviation of the

pain response in GlyR-HSV-treated mice was reversed by the

subsequent addition of low concentrations of strychnine, a strong

GlyR-specific inhibitor, or antagonist.

According to Dr. Glorioso, these findings suggest that HSV-directed

expression of GlyR in peripheral neurons and subsequent selective

activation by glycine has the potential to be used therapeutically

not only for neuropathic pain management but a variety of pain

syndromes.

" The inability to effectively manage neuropathic pain associated

with injuries and illnesses is a growing national and international

problem. Gene therapy offers a more targeted, less toxic approach

for effectively managing this condition. It also is our hope that

targeted transgene delivery of GlyR may have even broader

implications for managing a number of chronic pain syndromes,

including pain resulting from shingles, arthritis and cancer, "

explained Dr. Glorioso.

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In addition to Dr. Glorioso, others involved in the study included

Cascio, Ph.D., Goss, Ph.D., Krisky, M.D., Ph.D.,

and Rahul Scrinivasin, M.D., Ph.D., all with the department of

molecular genetics and biochemistry, University of Pittsburgh School

of Medicine.