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'Unprecedented': Drug May Help Heal Damaged Spine

Researchers say they’ve developed a drug that may help heal a damaged spine — the first time any has been shown to help.
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Researchers say they’ve developed a drug that may help heal a damaged spine — the first time anything like a drug has been shown to help.

The drug works on nerve cells that are cut, sending connections across the break, and it helped injured rats move their back legs again and also gave them back control of their bladders.

"This recovery is unprecedented," said Jerry Silver, a neuroscience professor at Case Western Reserve University in Ohio who led the study.

Right now, there’s no good way to heal a broken spine. Sometimes people grow nerve cells back, but usually not. All the cures that are in the works require invasive surgery, whether it’s injections of stem cells, nerve tissue transplants or implants of neurostimulators.

But Silver’s team came up with a compound that is injected. It doesn’t require surgery.

“We’re very excited at the possibility that millions of people could, one day, regain movements lost during spinal cord injuries."

"There are currently no drug therapies available that improve the very limited natural recovery from spinal cord injuries that patients experience," said Lyn Jakeman, a program director at the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, which helped pay for the study. "This is a great step toward identifying a novel agent for helping people recover."

“We’re very excited at the possibility that millions of people could, one day, regain movements lost during spinal cord injuries,” Silver added.

One of the problems with repairing a crushed spine is scar tissue. The body grows a lot of it, and even if nerve cells try to send out little growths called axons across the breach, they get bogged down by the scar tissue.

The culprits are molecules called proteoglycans. They are covered with sugars, and like anything sugary, they are sticky and grab the delicate axons that nerve cells grow to connect to other nerves. "What we found is that when nerve fibers are damaged they have a receptor that can see those proteoglycan molecules and stick tightly to it. They stick so tightly they can’t move. It's like flypaper," Silver told NBC News.

Graduate students Bradley Lang and Jared Cregg came up with the idea to design a compound that would stop the nerve cells from "seeing" the sticky proteoglycans. They made one that fits into the nerve cell receptor, a kind of molecular docking port, so that it couldn't stick to the proteoglycan.

"I told them it would never work," Silver said. "It seemed to me farfetched at best." He didn't think that injecting a compound under the skin would help nerves elsewhere in the body. But it did.

They’ve named it intracellular sigma peptide, or ISP for short. Injected daily into rats whose spines were crushed, it helped 21 out of 26 of them to regain either some movement, or bladder control, or both, the team reports in the journal Nature.

"Our animals are not just walking a little bit better. When they respond, they walk a lot better," Silver said.

Image: A rat performs the ISP gridwalk test to gauge its coordination and balance.
A rat performs the ISP gridwalk test to gauge its coordination and balance.Bradley Lang / Case Western Reserve University

Bladder control is a big issue for people with spinal cord injuries. They are often incontinent or even lose the ability to urinate at all, forcing them to live with a permanent catheter.

"Most paralyzed patients can cope with the loss of movement in the legs but find the loss of genitourinary function (the dysfunction of the genital and urinary organs) severely debilitating and demoralizing," said. Dr Elizabeth Bradbury of King's College London, who was not involved with the study.

"Consequently, recovery of bladder, bowel and sexual function is almost always ranked higher in priority than the ability to walk again by spinal injured patients."

"Our animals are not just walking a little bit better. When they respond, they walk a lot better."

Recovery from a spinal cord injury is rare.

“For any spinal cord-injured patient today, it would be considered extraordinary to regain even one of these functions, especially bladder function," Silver said. He also thinks ISP may help in other diseases that cause scarring, such as heart attack or multiple sclerosis.

Silver cautions that the approach has only been tested in newly injured animals. "People are going to want to know if they can get out of their wheelchairs now," he said. That's a question the team has not answered.

And before the approach can be tested in people. they'll have to try it on a larger animal, such as a pig, Silver said.

Another caveat — the compound is injected and travels through the entire body. The team did not see any obvious side effects in the rats, but they will watch for that. "If you used it long-term, you could see side effects, but it’s only going to be used for a short amount of time," Silver said.