The effect of a novel inhibitor of mast cell activation on mediators, symptoms and nasal patency in allergic rhinitis*1

An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment

“…Recently a nasal allergen challenge study demonstrated that inhibition of that pathway reduces mediator release. 6 The current study, conducted in a park setting, is the first to demonstrate that R112 provides rapid amelioration of clinical symptoms widely attributed to IgE-mast cell-triggered airway inflammation. A park setting was chosen because of the demonstrated sensitivity of this model for proof of principle to evaluate short-term efficacy and onset of action of drugs used to treat allergic rhinitis.…”

“…All 3 trials demonstrated good tolerability of nasal R112 (Data on file; Rigel Inc). 6 The results of this and previous studies document that Syk-kinase inhibition can reduce allergic Nasal passage irritation 1 (0.6%) 0 (0.0%) Nasal passage ulceration 1 (0.6%) 0 (0.0%) Application site burning 2 (1.3%) 1 (0.6%) Epistaxis 1 (0.6%) 2 (1.3%) Nasopharyngeal irritation 1 (0.6%) 0 (0.0%) Rashes 0 (0.0%) 1 (0.6%) Facial swelling 0 (0.0%) 1 (0.6%) Palpitations 0 (0.0%) 1 (0.6%) Somnolence 2 (1.3%) 0 (0.0%) inflammation. These data also suggest that that R112 is a safe and effective novel agent to treat the symptoms of SAR and is worthy of further clinical investigation.…”

Dose dependence and time course of the immunologic response to administration of standardized cat allergen extract

“…23,24 ELISA kits from BD Pharmingen (San Diego, Calif) and R&D Systems (Minneapolis, Minn) were used to measure each nasal cytokine (IL-4, IL-5, and IFN-g) and serum TGF-b levels. Allergen-specific IgE and IgG4 were measured by Pharmacia CAP systems (Pharmacia Diagnostics, Uppsala, Sweden).…”

Allergy and asthma

“…For example, previous work suggested a critical role for the Syk tyrosine kinase in IgE receptor signaling, 14 and clinical trials with Syk inhibitors are already underway. 15 MacGlashan and Miura 16 showed that prolonged stimulation (>18 hours) of FceRI on human basophils resulted in marked reductions in Syk levels, probably because of ubiquitylation and degradation. The authors proposed that such alterations might lead to basophil desensitization and could be involved in clinically beneficial procedures, such as rush immunotherapy and drug desensitizations.…”