The Journal of Bone and Joint Surgery (American). 2010;92:396-403.
doi:10.2106/JBJS.I.00109
© 2010 The Journal of Bone and Joint Surgery, Inc.
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Glatiramer Acetate Immune System Augmentation for Peripheral Nerve Regeneration in Rat Crushed Sciatic Nerve Model

Shai Luria, MD1, Thanapong Waitayawinyu, MD1, James Conniff, BA1, H. Josette Morton1, Nicholas M. Nemechek1, Joshua A. Sonnen, MD2, Leonid I. Katolik, MD1 and Thomas E. Trumble, MD1

1 Department of Orthopaedics and Sports Medicine, University Medical Center, University of Washington School of Medicine, Box 356500, 1959 Pacific Street, Seattle, WA 98195-6500. E-mail address for S. Luria: shail{at}hadassah.org.il
2 Department of Pathology, Harborview Medical Center, University of Washington School of Medicine, Box 359791, 325 9th Avenue, Seattle, WA 98104-2499

Investigation performed at the University of Washington School of Medicine, Seattle, Washington

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the University of Washington Faculty Initiative Fund. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.

Background Protective antiself response to nervous system injury has been reported to be mediated by a T-cell subpopulation that can recognize self-antigens. Immune cells have been shown to play a role in the regulation of motor neuron survival after a peripheral nerve injury. The objective of the present study was to evaluate the effects of immune system augmentation with use of the antigen glatiramer acetate, which is known to affect T-cell immunity, on peripheral nerve regeneration.

Methods Wild-type and nude-type (T-cell-deficient) rats underwent crush injury of the sciatic nerve. Three and six weeks after the injury, the sciatic nerve was examined, both functionally (on the basis of footprint analysis and the tibialis anterior muscle response and weight) and histologically (on the basis of axon count).

Results Significantly greater muscle responses were measured after three weeks in the group of wild-type rats that were treated with glatiramer acetate (control limb:injured limb ratio, 0.05 for the glatiramer acetate group [n = 9], compared with 0.51 for the saline solution group [n = 8]; p < 0.05). Higher axon counts were also found in this group (control limb:injured limb ratio, –0.07 for the glatiramer acetate group [n = 10], compared with 0.29 for the saline solution group [n = 8]; p < 0.05). The nude-type rats showed no response to the intervention after three weeks but showed a delayed response after six weeks. A second dose of glatiramer acetate, delivered forty-eight hours after the injury, did not result in an improved response as compared with the control groups.

Conclusions We found that a single treatment with glatiramer acetate resulted in accelerated functional and histological recovery after sciatic nerve crush injury. The role of T-cell immunity in the mechanism of glatiramer acetate was suggested by the partial and late response found in the T-cell-deficient rats.

Clinical Relevance Peripheral nerve injury may result in severe loss of sensation, weakness, and pain. The recovery is usually not complete with the limited treatment options. The recruitment of an endogenous mechanism, the immune system, to better coordinate the regeneration of nerves after injury is a different approach to this difficult clinical problem.


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