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Johns Hopkins Pediatric

The Battle to Protect and Preserve Peripheral Nerves

Doorways to Discovery
November 11, 2014

Ahmet Hoke
Neuromuscular disease expert Ahmet Hoke is charged with energy, just like the nerve fibers he is trying to reconnect in accident victims and wounded war veterans. For decades, researchers have searched for ways to stimulate injured ends of peripheral nerves to regrow and wend their way to endpoints in muscle and skin. Hoke’s work in cell biology, stem cell research, nanotechnology and drug development is at the vanguard.

Injured nerves regenerate slowly—about 1 millimeter each day—and typically lose their bearing over time. Hoke and his colleagues want to accelerate the pace of regeneration and keep the nerve fibers on course. “As a clinician, I feel an urgency to improve patient care,” he says.

Working with the U.S. Department of Defense, Hoke and his bioengineering colleagues are developing nanotube technologies in which they fill tiny conduits with even tinier, spaghettilike nanofibers and surgically implant them at injury sites to guide wayward nerve fibers. In a concept similar to fertilizing a flower garden, the researchers supply the nanotubes with nutritional nerve growth factors and Schwann cells, which naturally guide nerve fibers.

Hoke is lighting up other areas in the neuromuscular field, too, with his research to find ways to eliminate peripheral neurotoxicity, a common side effect of chemotherapy. Because it causes patients to develop unpleasant and sometimes debilitating numbness and weakness in their limbs, peripheral neurotoxicity is a major dose-limiting side effect of many chemotherapeutic drugs. It affects up to 80 percent of patients who get chemotherapy.

Several years ago, Hoke set out to screen thousands of chemical compounds as possible neuroprotective agents.

“We spent about five years and finally found an antioxidant called ethoxyquin that prevented nerve damage in cells in the laboratory,” he says. He and translational medicine experts at Johns Hopkins are now developing an ethoxyquin therapeutic compound for testing in clinical trials in humans.

Noting it has the potential “to prevent nerve damage in millions of cancer patients every year,” Hoke says. “I envision it being used like drugs we currently give chemotherapy patients to prevent nausea.”

Challenge: To repair damaged peripheral nerves and prevent peripheral neurotoxicity in patients treated with cancer drugs.

Approach: Hoke is developing nanotube technology to guide regenerating nerves and a therapeutic compound to prevent chemotherapy-related nerve damage.

Progress: Unique nanotube technologies are being developed to guide injured peripheral nerves. An antioxidant for preventing nerve damage caused by chemotherapeutic drugs is nearing testing in humans.

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