NEW YORK (Reuters Health) - In diabetic mice, neurotrophin factor gene transfer using an inactivated herpes simplex virus (HSV)-based vector reverses established peripheral neuropathy and restores lost nerve function.
Dr. James R. Goss from the University of Pittsburgh reported his team’s achievement Tuesday at the 34th Annual Meeting of the Society for Neuroscience underway in San Diego.
Diabetic neuropathy is thought to be associated with a deficiency or dysfunction of certain neurotrophic proteins essential for the survival and proper functioning of neurons.
Dr. Goss and colleagues used recombinant replication-defective HSV to shuttle the genes for one of two neurotrophin factors -- nerve growth factor (NGF) or neutrotrophin-3 (NT-3) -- directly to sensory neurons.
“HSV is an ideal gene therapy vector for diabetic neuropathy because it infects sensory neurons in its wild-type state making it easy to target this vector to affected neurons,” he explained in a telephone interview with Reuters Health.
In the study, mice with streptozotocin-induced peripheral neuropathy as shown by decreased foot sensory nerve amplitude and sensitivity to heat received a single subcutaneous injection of either NGF- or NT-3-encoded HSV, control HSV, or no treatment.
Five weeks after inoculation, signs of diabetic neuropathy had disappeared in the animals receiving either NGF- or NT-3-encoded HSV gene therapy. Their foot sensory amplitude and heat sensitivity readings were comparable to healthy non-diabetic control animals without neuropathy.
In contrast, peripheral neuropathy was still present in the animals treated with the control vector or nothing at all.
Currently, there are no effective treatments to halt progression of neuropathy, let alone reverse the associated nerve damage.
The current study, which demonstrates gene therapy can reverse diabetic neuropathy, builds on a previous study in which Dr. Goss and colleagues showed that the same gene therapy approach could prevent the development of neuropathy in diabetic animals. (see Reuters Health report February 18, 2002)
With an eye toward clinical trials, the next step is to develop another line of HSV-based vectors that have additional deletions to make them safer, Dr. Goss told Reuters Health. “The vectors we used in the current study cannot replicate but they may have the ability to recombine with wild-type virus, so we have to eliminate that possibility before we think about clinical trials,” he explained.
MeSH Headings:Animal Diseases: Biological Therapy: Congresses: Disease Models, Animal: Health Care Economics and Organizations: Genetic Engineering: Genetic Techniques: Investigative Techniques: Organizations: Therapeutics: Gene Therapy: Analytical, Diagnostic and Therapeutic Techniques and Equipment: Diseases: Health CareCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
