Swiss scientists severed the spinal cords of a half-dozen rats and then implanted flexible electrodes into the lower part of their spinal cords. The animals were also given a type of drug known as a serotonin agonist, which Courtine says readies the spinal cord to communicate with the legs, an ability that’s depleted after an injury. With their weight supported by a harness, the rats were placed on a treadmill or on a runway with obstacles.
This spring, doctors and researchers from the University of Louisville and the University of California, Los Angeles, said four men who had been paralyzed for years were able to regain movement in their legs, hips, ankles, and toes, and even stand using an implanted device that stimulated their spinal cords, a technique called epidural stimulation.
Though the movements achieved were modest—and fall short of allowing the men to walk on their own—the technology let them exercise their legs, which seemed to restore some movement.
A limit to epidural stimulation so far is that the electrical pulses don’t produce complex, coӧrdinated movement. Also, in human tests, the stimulators are controlled manually. That’s where the system Courtine developed could come into play. By filming the rats as they walked, the Swiss team fed the images to software that quickly adjusted the pattern of stimulation to produce synchronized stepping movements.
Such a system could help a person walk rhythmically and maintain his balance.
“This is the first closed-loop control system that can really adjust leg movements in real time, despite paralysis,” Courtine says. Each of the rats walked at least a thousand successive steps and successfully navigated rodent-sized stairs.
Courtine says his group is working on developing a brain-machine interface, such as electrodes implanted in the motor cortex of the brain to record intended movements, that might eventually allow patients to control a spinal stimulator, and the movement of their legs, using their own thoughts.
Neuromodulation of spinal sensorimotor circuits improves motor control in animal models and humans with spinal cord injury. With common neuromodulation devices, electrical stimulation parameters are tuned manually and remain constant during movement. We developed a mechanistic framework to optimize neuromodulation in real time to achieve high-fidelity control of leg kinematics during locomotion in rats. We first uncovered relationships between neuromodulation parameters and recruitment of distinct sensorimotor circuits, resulting in predictive adjustments of leg kinematics. Second, we established a technological platform with embedded control policies that integrated robust movement feedback and feed-forward control loops in real time. These developments allowed us to conceive a neuroprosthetic system that controlled a broad range of foot trajectories during continuous locomotion in paralyzed rats. Animals with complete spinal cord injury performed more than 1000 successive steps without failure, and were able to climb staircases of various heights and lengths with precision and fluidity. Beyond therapeutic potential, these findings provide a conceptual and technical framework to personalize neuromodulation treatments for other neurological disorders.
Related spinal cord repair
An array of techniques – some available now and others on the horizon – aim to restore movement and other functions in patients with spinal cord injuries.
In addition to the bioengineering approaches, researchers also have been looking at drug therapies and regenerative approaches for addressing paralysis due to spinal cord injuries. According to Mary Bartlett Bunge, professor of cell biology, neurological surgery and neurology at the University of Miami’s Miami Project to Cure Paralysis, about 1,275,000 Americans are affected by paralysis due to spinal cord injury and about 12,000 new cases occur each year in the United States.
China will probably have 1 million people with spinal cord injury in 2020 (80,000 per year). One third of the spinal cord injury people in the world. The US has about 10,000 spinal cord injury patients per year. Wise Young, MD, PhD Professor and Chair, Department of Cell Biology and Neuroscience, Rutgers University Director, W.M. Keck Center for Collaborative Neuroscience presented a talk at the March 2008 Spinal Cord Workshop: “Spinal Cord Injury: What are the barriers to cure?”
In 2014, Dr. Wise Young of the W.M Keck Center for Collaborative Neuroscience at Rutgers University said several first-generation drugs do show some efficacy in treatment of spinal cord injury. Methylprednisolone (MP) can improve motor and sensory function by 20% when given within eight hours of the injury, he said, and monosialic ganglioside (GM1) can speed recovery from a partial spinal cord injury if given within 48 hours. Another drug, 4-aminopyridine, improves conduction in nerve fibers that have lost their insulating myelin sheaths, Young said, but it has yet to be shown effective in treating spinal cord injury.
Young described his very promising work with mononuclear cells drawn from umbilical cord blood.
The cord blood cells are a source of various stem cells that can be useful in the repair and regeneration of tissues. Young and his colleagues at the China Spinal Cord Injury Network (ChinaSCINet) transplanted the cells into 20 patients in the Chinese city of Kunming who averaged 7 years after complete spinal cord injury. The cells were transplanted into the spinal cord above and below the injury site.
The patients received intensive walking training (six hours a day, six days a week for six months) in addition to the cell transplants. Within six to twelve months, Young said, 15 of the 20 patients were able to walk at least 10 meters with minimal assistance. Two of them could walk using only a four-point walker and no manual assistance. In addition, 12 of them no longer required assistance getting into and out of a wheelchair and getting onto the toilet. The results were better than expected, Young said, and additional clinical trials are planned.
Another promising approach was described by Bunge of the University of Miami, who has been working for four decades to understand Schwann cells, which provide support and protection for nerve fibers in the peripheral nervous system. She and her late husband, Dr. Richard Bunge, proposed that Schwann cells could be a key to helping repair damaged spinal cords.
“Schwann cells promote regeneration in peripheral nerves of the arms and legs,” Bunge said. “Why not tin the spinal cord?”
In painstaking studies with rats, Bunge and her colleagues have shown that when Schwann cells are implanted in the spinal cord, they can form myelin around regenerated nerve fibers, or axons. The studies also showed some improvement in the animals’ ability to walk after paralysis. Bunge said a triple combination strategy, using a variety of growth factors and an enzyme to reduce scar tissue along with the Schwann cells, is one way to improve the repair process. The combination produces “myriads of myelinated axons,” Bunge said.
Related Body Transplants
SOURCES – Technology Review, Science Translational Medicine, American Association for the Advancement of Science