Mast cell mediators as targets of treatment
MC-targeted treatments are primarily developed for chronic urticaria
(CU), mastocytosis, and allergies, because of the critical role that MCs
play in their pathogenesis 65,96. The evolution of
MC-targeted treatments started, more than 70 years ago, with the
development of drugs that inhibit the effects of individual MC
mediators, first histamine, followed by prostaglandins and leukotrienes97. Modern antihistamines that act on the histamine 1
receptor are superior to first generation ones in their binding
affinity, specificity, and risk/benefit profiles. Antihistamines that
act on the histamine 4 receptor have shown promising results, and
several such compounds are currently being developed for the treatment
of MC-driven diseases. Recently a new approach to inhibit tryptase, the
major MC protease, with an anti-tryptase antibody was tested in
preclinical primate studies 98. The therapeutic area
is initially severe asthma where MCs are implicated99.
However, to target one MC mediator or one of its receptors comes with an
inherent limitation, i.e., it prevents only the effects of one MC
mediator or receptor. Activated MCs release many different mediators
(acting on even more receptors) that are held to contribute to the
development of signs and symptoms in patients with urticaria,
mastocytosis and other MC-mediated diseases.