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Scientists use gene transfer technology and common virus to block neuropathic pain

t. Our goal is simply to deliver a gene to sensory nerve cells, so its product can be used to block transmission of pain signals from damaged nerves to the brain."

After removing genes that make it possible for the herpes simplex virus to infect a human host, VA/U-M scientists use it as a carrier to deliver GAD to the nucleus of nerve cells in the dorsal root ganglion near the spine. In previous studies, the researchers have confirmed that the vector remains in the dorsal root ganglion, but an enzyme expressed by the GAD gene moves to nerve terminals in the spinal cord where it triggers production of a powerful neurotransmitter called GABA.

"GABA is the main inhibitory neurotransmitter in the nervous system," Fink says. "It's like a hall monitor for the nervous system; it damps down neurotransmission between cells to keep things quiet. You can't have every neuron talking to every other neuron all the time or you'd have chaos."

Other scientists have shown that decreased GABA activity in the spinal cord contributes to the development of neuropathic pain, according to Fink.

Physicians have drugs that block neural transmission by mimicking the actions of inhibitory agents like GABA, but it's difficult to give these drugs in adequate doses, because the same drug that blocks pain also interferes with brain activity, leaving people drowsy and unable to think clearly.

"What we need is a way to release GABA in the spinal cord where it can selectively block incoming pain signals from peripheral nerves," says Fink. "If we can block transmission of the signal at the first neural synapse, it will never reach the brain and you won't feel pain."

That's where the herpes-based vector comes in. Although scientists can use many kinds of vectors to transfer genes into living cells, HSV has a natural ability to travel long distances along nerve fibers to reach the neural cell's nucleus, which makes it the perfect gene delivery vehicle for
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Source:University of Michigan Health Systems


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