The demonstrated role of L-selectin in the development of pathology in numerous autoimmune and inflammatory disorders makes it an attractive therapeutic target. However, despite a wealth of successes using blockade of L-selectin function in ani mal models of disease, few of these successes have translated to humans. Recently, pan-selectin antagonists have received attention for their ability to reduce leukocyte infiltration to diseased tissues by competing with selectins for ligand binding. Specifically, bimosiamose, developed by Kogan et al., a low molecular weight nonoligosac-charide selectin inhibitor, prevents P-, E-, and L-selectin-mediated adhesion in vitro [262, 263]. Additional in vivo studies suggest that bimosiamose does not inhibit leukocyte rolling but functions primarily by blocking E-selectin-mediated adhesion . Recent limited clinical trials using bimosiamose have shown some promise. Specifically, patients with mild allergic asthma treated with inhaled bimosiamose had a 50% reduction in late asthmatic reactions following allergen challenge . Similarly, psoriatic patients treated with bimosiamose, demonstrated reductions in epidermal thickness and lymphocyte infiltration . In addition to pan-selectin antagonists, specific blockade of L-selectin function using humanized anti-L-selectin mAbs (HuDREG-55 and HuDREG-200) is being explored . Specifically, the HuDREG-55 mAb (aselizumab) was found to significantly decrease mortality and increase survival time in a baboon model of hemorrhagic-traumatic shock . However, no significant benefit of aselizumab treatment was found in a Phase II clinical trial of patients suffering from sustained trauma due to blunt or penetrating injury . Another possible therapeutic strategy is the targeting of selectin ligands. Support for this comes from studies by Rosen et al. , demonstrating that blocking L-selectin ligands using MECA-79 mAb treatment results in decreases in late-phase airway responses and airway hyperresponsiveness following airway allergen challenge in a sheep model of asthma. Therefore, despite some promising initial results, whether or not selectin-based therapies will provide efficacious treatment for human disease remains to be determined.
Was this article helpful?
If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.