Researchers for the first time have induced robust regeneration of nerve connections that control voluntary movement after spinal cord injury, showing the potential for new therapeutic approaches to paralysis and other motor function impairments.

In a study on rodents, the UC Irvine, UC San Diego and Harvard University team achieved this breakthrough by turning back the developmental clock in a molecular pathway critical for the growth of corticospinal tract nerve connections.

They deleted an enzyme called PTEN (a phosphatase and tensin homolog), which controls a molecular pathway called mTOR that is a key regulator of cell growth. PTEN activity is low early during development, allowing cell proliferation. PTEN then turns on when growth is completed, inhibiting mTOR and precluding any ability to regenerate.

Trying to find a way to restore early-developmental-stage cell growth in injured tissue, Zhigang He, a senior neurology researcher at Children’s Hospital Boston and Harvard Medical School, first showed in a 2008 study that blocking PTEN in mice enabled the regeneration of connections from the eye to the brain after optic nerve damage.

He then partnered with Oswald Steward of UCI and Binhai Zheng of UCSD to see if the same approach could promote nerve regeneration in injured spinal cord sites. Results of their study appear online inNature Neuroscience.

“Until now, such robust nerve regeneration has been impossible in the spinal cord,” said Steward, anatomy & neurobiology professor and director of the Reeve-Irvine Research Center at UCI. “Paralysis and loss of function from spinal cord injury has been considered untreatable, but our discovery points the way toward a potential therapy to induce regeneration of nerve connections following spinal cord injury in people.”

According to Christopher & Dana Reeve Foundation data, about 2 percent of Americans have some form of paralysis resulting from spinal cord injury, which is due primarily to the interruption of connections between the brain and spinal cord.

He and his colleagues are now studying whether the PTEN-deletion treatment leads to actual restoration of motor function in mice with spinal cord injury. Further research will explore the optimal timeframe and drug-delivery system for the therapy.

More info: University of California – Irvine news