Issue Date: June 16, 2010
Antibodies Aid Nerve Repair
Antibodies are crucial for successful regeneration after nerve damage, reports a team led by Stanford University School of Medicine neurobiologist Ben A. Barres (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1001948107).
The finding may explain why nerve damage in the central nervous system (CNS), which lacks antibodies, isn't naturally repaired. By contrast, circulating antibodies can gain access to and help repair damage in the peripheral nervous system (PNS), which consists of nervous tissue outside the brain and spinal cord, such as the sciatic nerve.
When the researchers began their study, they knew that myelin, a fatty insulator that coats the axon of nerve cells, is cleared rapidly from damaged nerves in the PNS but not the CNS. They also knew "the blood-nervous system barrier rapidly breaks down after PNS but not CNS injury," Barres says, enabling serum proteins to enter the degenerating nerve.
When the researchers assessed mutant mice that did not make antibodies, they found PNS myelin clearance was dramatically delayed. "In addition, the regenerative nerves grew back significantly slower," Barres says. "These findings show that degenerating myelin is strongly inhibitory to regenerating axons." Injecting the mice with an antimyelin antibody restored rapid myelin clearance.
"This is really important, elegant work," comments Zhigang He, a Harvard Medical School neurologist who studies nervous tissue regeneration. "Everybody's trying to understand what accounts for the difference between the capacities for repair in the peripheral versus the central nervous system. Now we have a possible mechanism, so we can start to think about some kind of strategy to speed up myelin clearance in the brain."
The results "imply that antibodies that target degenerating CNS myelin may be able to help clear degenerating CNS myelin, which otherwise will remain in the CNS forever, where it will continue to inhibit axon regeneration," Barres says.
Antibodies could be delivered to the CNS by injecting them into the cerebrospinal fluid, Barres says. "Alternatively, new ways are being developed to modify the antibody so that it can sneak into the brain across the blood-brain barrier," he adds, though "that has not been successfully done yet." Such methods could conceivably be used to treat conditions including stroke and spinal-cord trauma.
- Chemical & Engineering News
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