Dry eyedisease compounds…
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CIS-‐UROCANICACID
LaurantisPharma Ltd and Kuopio University Hospital are developing eye
drops containing Cis-‐urocanic acid (cis-‐UCA) as treatment for ocular surface
inflammation associatedwithmoderate to severe dry eye syndrome. Cis-‐urocanic
acid inhibits the SAPK/JNK signaling pathway in ultraviolet B (UV-‐B) exposed
human corneal epithelial cells
in vitro,
having important implications in the
management of inflammatory eye conditions since chronic stress is directly linked
tocytotoxicity inepithelial cells. During tests itwasdemonstrated that is inhibiting
the secretionof pro-‐inflammatory cytokines fromhuman conjunctival and corneal
epithelial cells after UV-‐B-‐induced stress reaction (49, 50). Preclinical studies in
relevant animal models of eye inflammation also demonstrated that cis-‐UCAmay
be a safer andmore effective alternative to current drugs used for acute and long-‐
termtreatment of dryeye. FromNovember2011toMay2012Laurantis conducted
Phase I (ClinicalTrials.gov Identifier: NCT01476332), safety, tolerability and
pharmacokinetics studies of 0.5% and 2.5% Cis-‐UCA eye drops in adult healthy
volunteers. The results are not published, but the company continues the
development of thecompound.
THYMOSINBETA4
RegeneRx Biopharmaceuticals is developing RGN-‐259 which is a 0.1%
Thymosin Beta 4 (Tβ4) ophthalmic solution as a novel therapeutic treatment for
dry eye (51, 52). Thymosin Beta 4 is a synthetic version of a naturally occurring
peptide, used clinically as a tissue repair and regenerationpeptide (53). Inhuman
body is a protein encoded by the TMSB4X gene (GenBank accession number:
NC_000023.10). During preclinical evaluations it was demonstrated that Tβ4 is
promoting corneal epithelial intercellular adhesions following injury in animal
models of dry eye (54). In June2011RegeneRx startedPhase II safety andefficacy
studies (ClinicalTrials.gov Identifier: NCT01387347) of the RGN-‐259 ophthalmic
solution in patients with dry eye syndrome. The study has been completed in
December 2012 and in ARVO 2012 the company presented the results, claiming
the statistically significant reduction in central corneal fluorescein staining from
baseline compared to placebo and also a greater reduction in exacerbation of
oculardiscomfort (55).
