Mechanisms of LtxA (Leukotoxin), a Potent New Anti-Inflammatory Agent for the Treatment of Alopecia Areata

J Investig Dermatol Symp Proc. 2015 Nov;17(2):19-22. doi: 10.1038/jidsymp.2015.34.

Abstract

Alopecia areata is an autoimmune condition where activated, pro-inflammatory white blood cells (WBCs) attack the hair follicles, resulting in hair loss. Migration of these activated WBCs from the blood stream and into the follicle tissue requires interaction between the integrin, lymphocyte function-associated antigen-1 (LFA-1) on WBCs, and ICAM-1 on vascular endothelial cells. High levels of active LFA-1 are uniquely expressed on WBCs that are involved in autoimmune and inflammatory conditions. The natural biologic agent LtxA (Leukothera) preferentially targets and depletes disease activated and malignant WBCs by binding to active LFA-1. The experimental drug has demonstrated significant therapeutic efficacy against autoimmune/inflammatory conditions such as psoriasis and allergic asthma in mouse models for these diseases. In addition, when injected into rodents, rhesus macaques, and dogs, LtxA was demonstrated to be physiologically active, biologically specific, and extremely well-tolerated. LFA-1 is an attractive target for therapy because it is only normally present on WBCs and has been shown to be activated and overexpressed on WBCs that are responsible for autoimmune/inflammatory conditions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alopecia Areata / drug therapy*
  • Alopecia Areata / immunology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Autoimmune Diseases / drug therapy*
  • Cell Death / drug effects
  • Exotoxins / pharmacology*
  • Exotoxins / therapeutic use
  • Humans
  • Leukocytes / drug effects*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Exotoxins
  • leukotoxin