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Review
. 2012 Sep;130(3):563-71.
doi: 10.1016/j.jaci.2012.07.027.

Novel targeted therapies for eosinophilic disorders

Michael E Wechsler  1 , Patricia C Fulkerson, Bruce S Bochner, Gail M Gauvreau, Gerald J Gleich, Tim Henkel, Roland Kolbeck, Sameer K Mathur, Hector Ortega, Jatin Patel, Calman Prussin, Paolo Renzi, Marc E Rothenberg, Florence Roufosse, Dagmar Simon, Hans-Uwe Simon, Andrew Wardlaw, Peter F Weller, Amy D Klion
Affiliations
Review

Novel targeted therapies for eosinophilic disorders

Michael E Wechsler et al. J Allergy Clin Immunol. 2012 Sep.

Abstract

Hypereosinophilic syndromes (HESs) are a diverse group of conditions characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. HESs are chronic disorders with significant morbidity and mortality. Although the availability of targeted chemotherapeutic agents, including imatinib, has improved quality of life and survival in some patients with HESs, additional agents with increased efficacy and decreased toxicity are sorely needed. The purpose of this review is to provide an overview of eosinophil biology with an emphasis on potential targets of pharmacotherapy and to provide a summary of potential eosinophil-targeting agents, including those in development, in clinical trials, or approved for other disorders.

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Conflict of interest statement

Disclosure of potential conflict of interest: M. E. Wechsler has received research support from the National Institutes of Health (NIH); has received consulting fees from GlaxoSmithKline, Cephalon, Novartis, Sepracor/Sunovion, Schering-Plough, NKT Therapeutics, Asthmatx/BSCI, Genzyme, MapPharma, Genentech, and Boehringer Ingelheim; and has received honoraria from Merck. B. S. Bochner has received grants from the National Institute of Allergy and Infectious Diseases and the National Heart, Lung, and Blood Institute; has consultant arrangements with Sanofi-Aventis, Genentech, Merck, Roche, GlaxoSmithKline, TEVA, GlycoFi, and Medicis; is on a scientific advisory board for Merck; is a coinventor on existing and pending Siglec-8–related patents; might be entitled to a share of royalties received by his university on the potential sales of Siglec-8–related products but thus far has received no such royalties; receives royalties from UpToDate and Elsevier; is a cofounder of and has purchased stock in Allakos; and holds stock options for Glycomimetics. G. M. Gauvreau has received research support from Topigen Pharma. G. J. Gleich is a board member of the American Partnership for Eosinophilic Disorders (APFED) without compensation; has received consultancy fees from GlaxoSmithKline; has received research support from TRIA Bioscience Corp and ImmViz; has a patent with ImmViz; has received royalties from Teva; and has stock/stock options in Immune Design Corp. T. Henkel has received consultancy fees from Cephalon and is employed by and has received stock/stock options in Ception Therapeutics. R. Kolbeck is employed by and owns stock/stock options in MedImmune. S. K. Mathur has received consultancy fees from Teva Pharmaceuticals, is employed by the University of Wisconsin and William S Middleton VA Hospital, and has received research support from the NIH. H. Ortega is employed by and has received stock/stock options in GlaxoSmithKline. P. Renzi has received research support, consulting fees, and fees for participation in review activities from Pharmaxis and has received royalties and owns a patent as the inventor of TPI-ASM8. M. E. Rothenberg is a member of the board for APFED and the International Eosinophil Society, has received consultancy fees from Immune Pharmaceuticals, is the inventor of patents owned by Cincinnati Children’s, and has stock/stock options in Immune Pharmaceuticals and Teva. F. Roufosse has received consulting fees and travel support from GlaxoSmithKline and received royalties from UpToDate Online. D. Simon has provided expert testimony for Basilea Pharmaceutica and Astellas Schweiz, has received research support from OPO Foundation Zurich, and has received lecture fees from Basilea Pharmaceutica. H.-U. Simon has received consultancy fees from Pfizer. P. F. Weller has received consultancy fees from GlaxoSmithKline and receives royalties from UpToDate. A. Wardlaw was a member of the Cephalon-Teva data monitoring board; has received research support from Pfizer and GlaxoSmithKline; and has provided legal consultation/expert witness testimony for Bayer. The rest of the authors declare that they have no relevant conflicts of interest.

Figures

FIG. 1
FIG. 1
Active and theoretic eosinophil-selective therapeutic targets. The eosinophil possesses multiple targets that are the focus of active research in patients with hypereosinophilic diseases. These include IL-5, CCR3, Siglec-8, EMR1, CRTH2, cysteinyl leukotriene 1 (CYSLTR1), and the gluco-corticoid receptor (GR). Multiple other targets on the eosinophil and in pathways indirectly related to the eosinophil exist and are not depicted in this image. Medical Illustrator Jacqueline Schaffer provided this work.
See this image and copyright information in PMC

References

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