The Quest for Nerve Regeneration

When peripheral nerves—the long nerve fibers that reach from the spinal cord to control muscles and report sensations—are damaged by underlying conditions such as diabetes or traumatic injury, the result can be a torment of “pins and needles” pain.

And because therapies for the condition, known as peripheral neuropathy, are aimed only at controlling symptoms, not the root cause, many patients are left with a long-lasting disability.

Now, Johns Hopkins’ peripheral nerve group, led by Ahmet Höke, is working to develop novel drugs that can prevent nerve fibers from degeneration and even accelerate regeneration.

Already, the team has developed a cell type with all the properties of a sensory neuron, the basic nerve cell of the peripheral nervous system. Using this sensory neuronal cell line, they’ve screened about 2,000 FDA-approved compounds. Eventually, they’ll screen more than 100,000 through Hopkins’ ChemCore, a state-of-the-art robotics facility where researchers simultaneously screen multiple compounds found in large chemical libraries.

Agents found to be successful will be tested in animal models of peripheral neuropathies and then in patients undergoing chemo?therapy. Why chemo? The powerful drug cocktails can cause painful neuropathies, precluding oncologists from using higher doses. “That’s a big limiting step,” says Höke. “If we could come up with a drug that ameliorates the neuropathy, and administer it when we give chemotherapy, then we could use higher, more effective doses of chemo."

But the hard part, says Höke, lies not so much in preventing nerve degeneration as in regenerating nerves once they’ve been injured. Multiple interventions have been shown to improve nerve regeneration in small animals. In humans, however, that has not been the case, in part because nerves must regrow over longer distances.

Today, the prospect of molecular therapies that enhance nerve regeneration holds enormous promise and excitement. Such therapies could help those injured in accidents or wounded in war. Furthermore, Höke says, because neurodegeneration is common in many neurological disorders, including those of the central nervous system like Parkinson’s, MS and ALS therapies designed to accelerate peripheral nerve growth could very well speed central nerve growth as well.

Not surprisingly, nerve regeneration is a principle focus of Hopkins’ Brain Science Institute, an interdisciplinary endeavor established to accelerate the translation of discoveries into therapies. Led by Jack Griffin, formerly director of Neurology, it draws together scientists, engineers and others engaged in translational basic neuroscience research from all over the University.