Disrupting kinase cascades
Immune reactions, such as allergic conjunctivitis, occur as a series of cellular events, all of which represent points of therapeutic intervention. One of these points is the IgE receptor-triggered, mast-cell degranulation and histamine release that is catalyzed by spleen tyrosine kinase (Syk).2
Syk inhibitors have been touted as potential therapies for blood cell cancers, allergic asthma, and allergies in general. There are a number of small molecule, Syk-targeted compounds in clinical stage testing, and trials involving allergic disorders are expected in the near future.
Kinases are key metabolic regulators and it is not surprising that many kinase inhibitors have therapeutic potential. Drugs–such as Imatinib (Gleevec, Novartis), an important therapy for chronic leukemias and stromal tumors–recently were shown to be an effective inhibitor of mast-cell growth–and a potential treatment for allergic asthma and other allergic conditions.3
Another kinase in the crosshairs is IkK-beta, a key player in pro-inflammatory signaling. Inhibitors of this kinase, such as SAR113945 (Sanofi), have been tested as treatments for osteoarthritis. Similar compounds may have a role in chronic allergy therapy.
Lastly, there is the potential for ROCK kinases inhibitors and the MAP kinases. Both are therapies for different disorders from glaucoma to various neoplasias. The focus of these molecular compounds are best suited to an empirical assessment of efficacy in ocular allergy and inflammation.
On a different front, efforts to unravel the mechanisms of action for compounds derived from natural products used as allergy treatments (such as flavonoids, stilbenes, and curcuminoids)4 have narrowed the focus to a common, mast-cell stabilization effect.
This was demonstrated by in vitro studies in basophilic cell lines. Given the common mechanism in several popular herbal preparations, a revival of interest in mast cell stabilizers may be on the horizon.