Neuroprotection in the PNS: Erythropoietin and Immunophilin Ligands

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Neuroprotective Agents: Seventh International Conference

Volume 1053 published August 2005

Ann. N.Y. Acad. Sci. 1053: 491–501 (2005).

Neuroprotection in the PNS: Erythropoietin and Immunophilin Ligands

AHMET HÖKE AND SANJAY C. KESWANI

Department of Neurology, s Hopkins University School of

Medicine, Baltimore, land, USA

Address for correspondence: Ahmet Höke, M.D., Ph.D., Department of

Neurology, s Hopkins University, 600 North Wolfe Street, Path

509, Baltimore, MD 21287.

Many illnesses that affect the peripheral nervous system (PNS) lead

to distal axonal degeneration rather than loss of neuronal cell

bodies. Strategies aimed at promoting survival of injured neurons

(i.e., preventing cell death) may not be applicable to many PNS

illnesses. We have developed in vitro and in vivo animal models to

study mechanisms of acquired peripheral neuropathies and used these

models to evaluate the therapeutic potential of novel compounds. In

recent years, erythropoietin (EPO) has been recognized as a novel

neuroprotectant in the central nervous system. In the PNS, we

recently showed that Schwann cell-derived EPO acts as an endogenous

neuroprotectant and that it is most effective in preventing distal

axonal degeneration seen in models of peripheral neuropathy.

Similarly, we showed that immunophilin ligands are also

neuroprotective in the PNS and prevent axonal degeneration seen in

models of peripheral neuropathies. Both EPO and non-

immunosuppressive immunophilin ligands are in early clinical

development for the treatment of acquired peripheral neuropathies.