Nerve Connections Regenerated after Spinal Cord Injury

www.uci.eduResearchers for the first time have induced vigorous regeneration of nerve connections that control voluntary movement after spinal cord injury, revealing the possibility for new therapeutic treatments for paralysis and other motor function impairments.

In a study on lab rodents, University of California (UC) Irvine (UCI; USA), UC San Diego (UCSD; USA), and Harvard University (Cambridge, MA, USA) investigators achieved this breakthrough by turning back the developmental clock in a molecular pathway vital for the growth of corticospinal tract nerve connections. They did this by deleting an enzyme called a phosphatase and tensin homolog (PTEN), 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, suppressing mTOR and preventing any ability to regenerate.

Trying to find a way to restore early-developmental-stage cell growth in injured tissue, Dr. Zhigang He, a senior neurology researcher at Children's Hospital Boston (MA, USA) and Harvard Medical School, first demonstrated 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 collaborated with Drs. Oswald Steward of UCI and Binhai Zheng of UCSD to see if the same approach could promote nerve regeneration in injured spinal cord sites.

"Until now, such robust nerve regeneration has been impossible in the spinal cord," said Dr. Steward, anatomy, and 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."

An injury the size of a grape can lead to complete loss of function below the level of injury. For example, an injury to the neck can cause paralysis of arms and legs, loss of ability to feel below the shoulders, inability to control the bladder and bowel, loss of sexual function, and secondary health risks including susceptibility to urinary tract infections, pressure sores, and blood clots due to an inability to move the legs. "These devastating consequences occur even though the spinal cord below the level of injury is intact," Dr. Steward noted. "All these lost functions could be restored if we could find a way to regenerate the connections that were damaged."

Dr. Steward and his colleagues are now assessing whether the PTEN-deletion treatment leads to actual restoration of motor function in mice with spinal cord injury. Additional research will explore the best timeframe and drug-delivery system for the therapy.


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University of California, Irvine

University of California, San Diego

Harvard University

Children's Hospital Boston