Neuroprotection in the PNS: erythropoietin and immunophilin ligands.
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.
Höke
Ahmet
A
Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Path 509, Baltimore, Maryland 21287, USA. ahoke@jhmi.edu
Keswani
Sanjay C
SC
D000818:Animals; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D020104:Immunophilins / Q000627:therapeutic use*; D008024:Ligands; D010523:Peripheral Nervous System Diseases / Q000473:pathology / Q000517:prevention & control*; D012583:Schwann Cells / Q000378:metabolism
D008024:Ligands; D004921:Erythropoietin; D020104:Immunophilins