New Tools for Spinal Cord Repair

Irvine, CA, August 12th, 2013 -- Spinal cord injuries are among medicine’s most complex challenges. Last week’s speaker at the SURF-IT lunchtime seminar series shared the progress his research team is making into repairing a particularly vexing form of spinal cord damage.

Injuries to the lower spine, known as the lumbar sacrum, comprise approximately 20 percent of all spinal cord damage. Home to a bundle of spinal nerves and spinal nerve roots known as cauda equina, these injuries often include motor, sensory and autonomic (bladder, bowel, sexual) dysfunction.

Dr. Leif Havton and his team at UC Irvine’s Gillespie Neuroscience Research Facility currently are repairing these injuries in primates with the goal of beginning clinical trials with humans in the not-so-distant future.

Havton, vice chair of the Department of Anesthesiology & Perioperative Care, and professor of anatomy & neurobiology, and neurology, said the lower part of the spine is particularly vulnerable to severe injury due to its S-shaped curvature. Most treatments developed over the past 15-20 years, however, have focused on injuries to the upper region of the spinal cord.

In the most severe type of injury, the nerve root separates completely from the surface of the spinal cord. Havton and his team are working to repair these injuries by reattaching the nerve roots into the spinal cord. 

The team, which includes SURF-IT student Timothy Vu, studies the electrical signals from the nerves and muscles in cauda equina injuries – both before and after surgery – to determine whether the post-surgery nerve cells are regaining their function.
 
They found initial success in rat studies, noticing not only that the repaired cells were regenerating but that more peripheral nerve cells were surviving as well. “This was very encouraging to us,” Havton said. “The weakness, numbness, pain, bladder and bowel problems can be studied and reversed to a large degree when we do the surgical repair.”

Spinal cord injury and repair, he told the SURF-IT audience, are relatively new research areas, so before proceeding to human clinical trials, his team decided to work with primates. In collaboration with the California National Primate Research Center at UC Davis, they are attempting to re-create their results in large mammals.

This phase of the research, Havton said, has three goals: learning whether these procedures are feasible in large mammals; determining whether the results from the rat studies can be duplicated; and training surgeons to perform the delicate operations. “We are working with neurosurgeons and spine surgeons because in the U.S., no surgeons have done this on a human being,” he said, adding that anatomically, the area is very challenging to operate on.

The team is using assessment models developed for humans. These include electromyography (EMG), urodynamic studies, physical therapy and imaging studies like MRI, which allow them to measure and understand to what degree the nervous system is functioning.

“We started from scratch, but have since developed the knowledge. Now we have a functional model where we can perform these studies in a clinically relevant fashion.”

Additionally, Havton explained, he is working with colleagues at Johns Hopkins University in Baltimore to develop biodegradable tubes, which can serve as conduits between the injured nerve roots and the spinal column. Severe spinal cord trauma often precludes the possibility of directly attaching the nerve roots to the spinal cord so the tubes could one day replace more invasive nerve graft surgery.

These tubes can be “dressed up” with different types of growth factors, optimizing the regeneration process. “We’re trying to figure out how different types of nerve fibers have a preference for different types of growth factors,” he said. “We want to customize these growth factors to attract the right kind of fibers to grow out.” 

A grant from the Department of Defense is allowing the research team to test this procedure in the primate population as well. Because the animals are followed over a long period of time post-surgery – nerve regeneration can take one to three years – the project involves massive datasets, and the team is seeking ways to manage those better.

“The [EMG] recordings are very helpful to us,” Havton said, adding that researchers are developing more sophisticated signal processing analysis techniques in an effort to quantify the data accurately and efficiently. 

“Different components of the EMG signals may mean different things. That’s why we’re interested in looking at these recordings from many different angles to best interpret the activity in a user-friendly fashion.”

The data will help researchers determine which approach to surgical repair is most efficacious; they also will provide screening tools for potential complications.
  
Vu’s role as a SURF-IT student on the project is to study the signals and help to design a user-friendly graphic user interface. “Tim is making it easier to interact between different software environments and develop different ways of presenting data and analyzing data efficiently and accurately,” Havton summarized.