Allergic conjunctivitis future or investigational therapies
Overview
Emerging therapies for allergic conjunctivitis include immunomodulators as well as evaluation of novel enzymatic targets.
Future or Investigational therapies
Calcineurin inhibitors
- They are capable of inducing local immunosuppression by blocking Th2 lymphocyte proliferation and IL-2 production and reducing eosinophils via inhibition of IL-5.
- Topical [1] and systemic cyclosporine a (CsA) [2] have been suggested in the treatment of severe atopic keratoconjunctivitis.
- Use of CsA appears to be safe and can eliminate the need/dependence of steroids.
- Others calcineurin inhibitors that appears to be well tolerated by patients with severe atopic blepharoconjunctivitis[3] and severe atopic keratoconjunctivitis are tacrolimus and pimecrolimus[4].
Mapracorat[5]
- Mapracorat is a novel selective agonist of the glucocorticoid receptor, resulting in a lower potential for side effect.
- In vitro, it inhibited migration and IL-8 release from eosinophils and the secretion of IL-6, IL-8, CCL5/RANTES, and TNF-α from a human mast cell line with equal potency as dexamethasone, but it was less potent in inducing annexin I and CXCR4 expression on the human eosinophils.
- Animal model of allergic conjunctivitis demonstrated mapracorat was similar to dexamethasone eye drops in analogous reduction of clinical symptoms and conjunctival eosinophil. Hence,studies suggest this compound as a candidate for clinical trials of ocular allergy.
- It is a biological engineered molecule, targeting the Cε3 domain of the IgE molecule. It binds with free IgE and prevents its attachment to high-affinity receptor (FcεRI) on mast cells, basophils and dendritic cells. An IgE-anti-IgE complex is formed, lowering free IgE[6].
- Omalizumab has been established for use in asthma[7] ,urticaria and and rhinitis[8].
- Clinical trials are needed to asses its real impact in ocular allergies.
Other developments[9]
- A novel target spleen tyrosine kinase (Syk) regulates the phosphorylation of phospholipase-C, phosphatidylinositol-3 kinase and protein kinase which mediate histamine release. Hence, studies will focus Syk inhibitors.
- Janus protein kinase-3 is involved in the activation and proliferation of T-cells. Thus, novel inhibitors of JAK-3 may be an effective therapy.
References
- ↑ Tzu JH, Utine CA, Stern ME, Akpek EK (2012). “Topical calcineurin inhibitors in the treatment of steroid-dependent atopic keratoconjunctivitis”. Cornea. 31 (6): 649–54. doi:10.1097/ICO.0b013e31822481c2. PMID 22378107.
- ↑ Cornish KS, Gregory ME, Ramaesh K (2010). “Systemic cyclosporin A in severe atopic keratoconjunctivitis”. Eur J Ophthalmol. 20 (5): 844–51. doi:10.1177/112067211002000506. PMID 20491051.
- ↑ Virtanen HM, Reitamo S, Kari M, Kari O (2006). “Effect of 0.03% tacrolimus ointment on conjunctival cytology in patients with severe atopic blepharoconjunctivitis: a retrospective study”. Acta Ophthalmol Scand. 84 (5): 693–5. doi:10.1111/j.1600-0420.2006.00699.x. PMID 16965503.
- ↑ Reynolds NJ, Al-Daraji WI (2002). “Calcineurin inhibitors and sirolimus: mechanisms of action and applications in dermatology”. Clin Exp Dermatol. 27 (7): 555–61. doi:10.1046/j.1365-2230.2002.01148.x. PMID 12464150.
- ↑ Baiula M, Spartà A, Bedini A, Carbonari G, Bucolo C, Ward KW; et al. (2011). “Eosinophil as a cellular target of the ocular anti-allergic action of mapracorat, a novel selective glucocorticoid receptor agonist”. Mol Vis. 17: 3208–23. PMC 3244483. PMID 22194647.
- ↑ Vichyanond P (2011). “Omalizumab in allergic diseases, a recent review”. Asian Pac J Allergy Immunol. 29 (3): 209–19. PMID 22053590.
- ↑ Holgate S, Buhl R, Bousquet J, Smith N, Panahloo Z, Jimenez P (2009). “The use of omalizumab in the treatment of severe allergic asthma: A clinical experience update”. Respir Med. 103 (8): 1098–113. doi:10.1016/j.rmed.2009.03.008. PMID 19362459.
- ↑ Casale TB, Busse WW, Kline JN, Ballas ZK, Moss MH, Townley RG; et al. (2006). “Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis”. J Allergy Clin Immunol. 117 (1): 134–40. doi:10.1016/j.jaci.2005.09.036. PMID 16387596.
- ↑ Mishra GP, Tamboli V, Jwala J, Mitra AK (2011). “Recent patents and emerging therapeutics in the treatment of allergic conjunctivitis”. Recent Pat Inflamm Allergy Drug Discov. 5 (1): 26–36. doi:10.2174/187221311794474883. PMC 3164156. PMID 21171952.
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