New Antiallergic Drugs

Abstract

Atopic diseases have been increasing in prevalence over the last few years and are becoming common causes of chronic health problems for patients of all ages. Current pharmacological treatments are targeted for symptom relief (antihistamines, decongestants, β-adrenergic agents, etc.) or for reduction of allergic inflammation (corticosteroids, leukotriene modifiers, etc.). The development of new therapies to treat allergic disease is now progressing into new areas of immune modulation such as regulating the allergic inflammatory response at the level of IgE (anti-IgE and anti-CD23) and inducing immunologic tolerance by shifting from the T helper (Th)2 to Thl phenotype (DNA vaccines). IgE plays a central role in the allergic inflammatory process; therefore, blocking the effects of IgE should be beneficial in the treatment of allergic diseases. At this time, a recombinant humanized monoclonal anti-IgE antibody has been synthesized that does not cause IgE receptor crosslinking on mast cells leading to de-granulation or immune complex deposition. Studies have been done to evaluate the effectiveness of anti-IgE in the treatment of allergic rhinitis and allergic asthma. One of the most significant endpoints of benefit was the ability to reduce the corticosteroid dose for moderate-to-severe allergic asthmatics. Another possible approach to reduce the effect of IgE in the inflammatory process would be to block CD23 (low-affinity IgE receptor, FcεRII), which plays a role in IgE synthesis and triggers the release of inflammatory cytokines. Little is known about the effectiveness of anti-CD23, but preliminary studies suggest it is safe. The use of immunostimulatory DNA to provoke a Thl phenotype has been an impetus for the development of DNA vaccines in the treatment of allergic disease. Various combinations of plasmid DNA, immunostimulatory oligodeoxynucleotide (ISS-ODN), and proteins have been studied in murine models to evaluate the effectiveness of DNA vaccination. The success in skewing the immune response towards a Thl phenotype in mice still needs to be evaluated in humans. The use of DNA vaccination as a treatment for allergic disease remains a viable option for the future; however, at this time further evaluation is needed including concerns regarding the possible unmasking or development of Thl diseases (lupus, rheumatoid arthritis, inflammatory bowel disease).