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Allergic conjunctivitis future or investigational therapies
Introduction
Overview
Overview
Emerging therapies for allergic conjunctivitis include immunomodulators as well as evaluation of novel enzymatic targets.
Future or Investigational therapies
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-Ξ± 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 CΞ΅3 domain of the IgE molecule. It binds with free IgE and prevents its attachment to high-affinity receptor (FcΞ΅RI) 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
References
- β Tzu JH, Utine CA, Stern ME, Akpek EK (2012). “Topical calcineurin inhibitors in the treatment of steroid-dependent atopic keratoconjunctivitis”. Cornea. 31 (6): 649β54. doi:10.1097/ICO.0b013e31822481c2. PMIDΒ 22378107.
- β Cornish KS, Gregory ME, Ramaesh K (2010). “Systemic cyclosporin A in severe atopic keratoconjunctivitis”. Eur J Ophthalmol. 20 (5): 844β51. doi:10.1177/112067211002000506. PMIDΒ 20491051.
- β 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): 693β5. doi:10.1111/j.1600-0420.2006.00699.x. PMIDΒ 16965503.
- β Reynolds NJ, Al-Daraji WI (2002). “Calcineurin inhibitors and sirolimus: mechanisms of action and applications in dermatology”. Clin Exp Dermatol. 27 (7): 555β61. doi:10.1046/j.1365-2230.2002.01148.x. PMIDΒ 12464150.
- β Baiula M, SpartΓ 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: 3208β23. PMCΒ 3244483. PMIDΒ 22194647.
- β Vichyanond P (2011). “Omalizumab in allergic diseases, a recent review”. Asian Pac J Allergy Immunol. 29 (3): 209β19. PMIDΒ 22053590.
- β 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): 1098β113. doi:10.1016/j.rmed.2009.03.008. PMIDΒ 19362459.
- β 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): 134β40. doi:10.1016/j.jaci.2005.09.036. PMIDΒ 16387596.
- β 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): 26β36. doi:10.2174/187221311794474883. PMCΒ 3164156. PMIDΒ 21171952.