Walking Ability Improves in Miami Paralysis Study

(May 27, 2004)

MIAMI (Reuters) - Rats with spinal cord injuries regained 70 percent of their normal walking function with a three-part treatment hailed as a breakthrough in paralysis research at the University of Miami School of Medicine.

The study at the university's Miami Project to Cure Paralysis, due to be published on Monday in the June issue of the journal Nature Medicine, produced results "by far greater than what we've seen in anything else," said the principal researcher, Dr. Mary Bartlett Bunge.

"It opens up a potential new avenue of treatment for human spinal cord injury," said Bunge, who declined to speculate when human trials might be attempted.

The spinal cord carries messages between the brain and the muscles through a network of nerve cells. Normally, chemical signals prevent those nerves from regrowing, resulting in paralysis when the network is severed by an injury.

Regrowing nerve cells and reconnecting them is the holy grail of spinal cord research.

The Miami study involved hundreds of animals with crushing injuries to the thoracic region of the spinal cord, which mainly causes loss of control of the legs and is the most common form of injury among the 243,000 people in the United States living with spinal cord injuries, the researchers said.

They transplanted cells known as Schwann cells from the peripheral nerves, where regeneration does occur, to create a bridge across the damaged area of the spinal cord and promote the growth of axons, the nerve fibers that transmit messages. Those cells also make the protective myelin sheath that insulates nerve fibers.

GROWTH STOPPED TOO SOON

In earlier research, such grafts did promote the growth of new nerve fibers across and through the damaged areas of the spinal cord, but they stopped growing too soon.

So researchers combined the grafts with two other treatments -- injections of cyclic AMP, a messenger molecule that guides the nerve cells to grow their connecting fibers, and Rolipram, which prevents the breakdown of cyclic AMP.

"The cyclic AMP hangs around longer and can be more effective," Bunge said in an interview on Friday.

Rolipram was developed as an antidepressant by Germany's Schering AG and is also being investigated as a possible treatment for multiple sclerosis.

After eight weeks, the rats that did not receive the treatment could occasionally take a halting step but could not take one step after another, Bunge said.

Those that received the treatment had regained 70 percent of their walking function, "a striking improvement," Bunge said. They could step consistently, and had better fine motor control and coordination.

"The hind limbs knew what the fore limbs were doing," said Bunge, who designed the study with her colleague, Dr. Damien Pearse.

The triple-treated animals also had more tissue in their spinal cords than those without the treatment, suggesting it had stopped the secondary tissue loss that normally occurs after a spinal cord injury, Bunge said. And the triple-treated rats had a 500 percent increase in nerve fibers in the graft area, she said.

"Each of the pieces of the (Miami) strategy have been hailed as 'promising' in earlier reports, but the behavioral effects were not huge. With the right combination, the sum is now proving to be much greater than the parts," said Dr. Naomi Kleitman, a program director for spinal cord injury research the National Institute of Neurological Disorders and Stroke, a component of the National Institutes of Health (news - web sites).