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Treating Small Fiber Neuropathy by Topical Application of a Small Molecule Modulator of Ligand-Induced GFRα/RET Receptor Signaling

Treating Small Fiber Neuropathy by Topical Application of a Small Molecule Modulator of Ligand-Induced GFRα/RET Receptor Signaling

Kristian L Hedstrom, Joshua C Murtie, Kathryn Albers, Nigel A Calcutt, Gabriel Corfas

Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2325-30.

PMID: 24449858

Abstract:

Small-fiber neuropathy (SFN) is a disorder of peripheral nerves commonly found in patients with diabetes mellitus, HIV infection, and those receiving chemotherapy. The complexity of disease etiology has led to a scarcity of effective treatments. Using two models of progressive SFN, we show that overexpression of glial cell line-derived neurotrophic factor (GDNF) in skin keratinocytes or topical application of XIB4035, a reported nonpeptidyl agonist of GDNF receptor α1 (GFRα1), are effective treatments for SFN. We also demonstrate that XIB4035 is not a GFRα1 agonist, but rather it enhances GFRα family receptor signaling in conjunction with ligand stimulation. Taken together, our results indicate that topical application of GFRα/RET receptor signaling modulators may be a unique therapy for SFN, and we have identified XIB4035 as a candidate therapeutic agent.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP529507844	XIB4035		529507-84-4	Price

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