An. Real. Acad. Farm. vol 80 nº 1 2014 - page 164

BasilioColligris, Jesús Pintor
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colleagues verified that DA-­‐6034 at concentrations above 100 microM increased
mucin-­‐like glycoprotein levels in animal models, in conjunctival and corneal
epithelial cells (79). Furthermore in human conjunctival epithelial cells, DA-­‐6034
treatment in doses of 200microM increasedmucin secretion between the trans-­‐
membrane mucins MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC16 (79). Seo
and colleagues investigated the inhibiting effect of DA-­‐6034 MMP-­‐9 on
inflammatory cytokines and the activation of the MAPK signaling pathway on
rabbit inflammationmodels. Itwas demonstrated that DA-­‐6034 could restore tear
function and inhibit inflammatory responses reducing the phosphorylation of Jun
N-­‐terminal kinase (JNK) andp38MAPK, inhibiting thenuclear factor kappaBcells
(NF-­‐kB) activation in corneal epithelial cells (80). TheNF-­‐κB is a key transcription
factor pathway, responsible for many key biological processes, such as
inflammation, apoptosis, stress response, cornealwoundhealing, andangiogenesis
(81). The companyDong-­‐A started a Phase II study of DA-­‐6034 (ClinicalTrials.gov
Identifier: NCT01670357) in January 2012 to determine the efficacy and safety of
3%or 5%DA-­‐6034 eye drops on 150 patients with doses of one drop/each eye,
four times/day, for fourweeks.
RX-­‐10045
Resolvyx Pharmaceuticals developed RX-­‐10045 (Figure 14) a small lipid
mediator as a product candidate for the treatment of ocular surface and anterior
segment diseases (82). In 2010 Celtic Therapeutics andResolvyx Pharmaceuticals
started to collaborate in the development of the compound. RX-­‐10045 is a
synthetic resolvinE1(RvE1) analog formulated for topical applicationtreatment of
eye disease as a potent mediator of inflammatory resolution, endogenously
producedby the humanbody fromomega-­‐3 fatty acid (83). Inpre-­‐clinical dry eye
models, RX-­‐10045 has demonstrated potent efficacy. The compound successfully
completedaPhase II study (ClinicalTrials.gov Identifier: NCT00799552) indryeye
patients and according to the companies it demonstrated significant symptom
improvement from baseline (as assessed in subject diaries), and performed
significantly better than placebo on the primary endpoint of the worst symptom
score with a 75% reduction in controlled adverse environment-­‐induced central
corneal staining frombaseline (84). RX-­‐10045was evaluated in another Phase II
study (ClinicalTrials.gov Identifier: NCT01675570) fromAugust 2012 to February
2013 on 150 patients for the treatment of dry eye disease but the results are not
yetpublished.
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