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University of Pittsburgh Researchers Present Findings at 10th Annual Meeting of the American Society of Gene Therapy, May 30 to June 3


Researchers from the University of Pittsburgh School of Medicine will present findings from more than 30 studies at the 10th annual meeting of the American Society of Gene Therapy, being held May 30 to June3 at the Washington State Convention & Trade Center, Seattle.

Note to reporters: Full press releases will be available Tuesday, May 29 on the EurekAlert! Web site, or by calling Jim Swyers at 412-657-4957.

Highlights of these studies include:


Gene Therapy Offers New Hope for Treatment of Peripheral Neuropathy

Embargoed until 3:45 p.m. PDT

Using a genetically engineered herpes simplex virus (HSV), University of Pittsburgh School of Medicine researchers delivered 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. After the delivery of the therapeutic gene, 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 sight of injection. Following formalin injection, the rats were then given an injection of glycine to activate the GlyR receptor. The application of glycine eliminated the pain response in GlyR-HSV infected animals, while it had no effect on control animals. According to the researchers, these findings suggest that HSV-directed expression of GlyR in peripheral neurons and subsequent selective activation by glycine has the potential to be used not only for the management of neuropathic pain but a variety of pain syndromes, including pain resulting from shingles, arthritis and cancer.

Virus Widely Used in Gene Therapy Research Yields Important Clues to GenomicInstability

Embargoed until 3:45 p.m. PDT

Genomic instability—the rearrangement of chromosomes or an abnormal number of chromosomes—is a hallmark of many human cancers. Researchers at the University of Pittsburgh School of Medicine have discovered that many of the sites where viruses used in many gene therapy experiments integrate into the host genome are the same sites where genomic instability is likely to occur. Specifically, they discovered that up to 30 percent of the integration sites occur in DNA palindromes—a sequence of base pairs in DNA that reads the same backwards and forwards across the double strands. A series of computer analyses revealed that these breakage-prone palindromes can be found throughout the genome, but only a subset of palindromes of a particular size are susceptible to breakage. These findings can contribute significantly to our understanding of the possible contributions to cancer and aging, according to the investigators.


Minicircle Plasmid Containing the Human Manganese Superoxide Dismutase TransgeneConfers Radioprotection to Cells In Vivo

Embargoed until 5:15 p.m. PDT

There is increasing concern that high-dose, whole body irradiation commonly given to patients with blood and lymphatic cancers may have long-term negative effects on healthy tissues and organs, such as the liver, kidneys and thyroid gland. University of Pittsburgh School of Medicine researchers, collaborating with scientists from Stanford University, have developed a new, smaller gene therapy vector for delivering the radioprotective enzyme, manganese superoxide dismutase, systemically throughout the body so that healthy tissue is spared the long-term effects of therapeutic irradiation. In cells in culture, the new delivery vector was as effective as an earlier version that was too large to be delivered systemically. This study was done in preparation for a human clinical trial of the new delivery method.


Gene Therapy Delivery of Nerve Growth Factors Reverses Erectile Dsyfunctionin Animal Model

Embargoed until 5:15 p.m. PDT

University Pittsburgh School of Medicine researchers injected rats that have erectile dysfunction (ED) very similar to human cases with a gene therapy vector containing either of two nerve growth factors. Four weeks after gene therapy, the rats that received the nerve growth factors regained normal penile function. According to the investigators, this represents the first-ever demonstration of a long-term treatment for ED that does not rely on administering drugs that can have potentially harmful side effects.


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