Enhancing Nerve Repair in GBS and CIDP
Kazim A. Sheikh, M.D., Department of Neurology, University of Texas Health Sciences Centre, Houston, TX

Guillain-Barre syndrome (GBS) and Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are considered to be organ specific immune disorders resulting from synergistic actions of cellular and humoral autoimmune responses directed against peripheral nerve antigens. Current therapies for the treatment of these conditions are directed at modulating abnormal autoimmune responses. The recovery process in both disorders requires curtailment of autoimmune injury and nerve repair. The natural nerve repair process is often very slow and incomplete and patients are left with residual deficits. The patients with residual damage almost always have failure of axon regeneration and reconnection with targets such as muscle or skin. We have found that immune effectors including some autoantibodies interfere with the process of axon regeneration. Our latest studies indicate that nerve damage induces expression of new injury-related proteins that are not expressed in normal nerves. Some of these proteins serve as receptors to capture immune molecules such as antibodies to form molecular complexes that interact with injured axons attempting to regenerate and prevent the process of nerve repair. The deleterious effects of the immune molecules on nerve repair are enhanced due to the formation of these complexes, which allow the immune molecules to stay in the nerve compartment for longer and also allow them interact with their target molecules more effectively.

There is lot of interest in developing new therapies that can enhance nerve repair and taking them to the clinical arena. Our group is also examining at new approaches that can enhance nerve repair to treat neuropathic conditions such as GBS and CIDP. In our initial studies we have found that recombinant human erythropoietin (EPO), an FDAapproved drug, significantly enhances nerve repair in preclinical models of autoimmune neuropathy. We are now in the process of generating genetically engineered modified forms of EPO that would allow the modified-EPO to interact with the same new proteins that are expressed in injured nerves and capture immune molecules such as antibodies to form complexes (see above). We believe that the modified-EPO will be captured by injury-related proteins expressed in the nerve to form complexes and this will allow modified EPO to stay longer in the nerve compartment and interact more avidly with its receptors to enhance axon regeneration/nerve repair more effectively than na?ve unmodified EPO. These GBS and CIDP Foundation sponsored studies are currently being carried out in our laboratory.

Acknowledgements: Sponsors GBS/CIDP Foundation International