Dry eyedisease compounds…
165
TOBRADEX
TobraDex
was approvedbyFDAasdryeye treatment in1988.
TobraDex
is a
combination of tobramycin and dexamethasone (Figure 15). Tobramycin is an
aminoglycosideantibiotic-‐antibacterial derived fromstreptomycestenebrarius and
is used to treat various types of eye infections. It is working through binding to a
site on the bacterial 30S and 50S ribosome, preventing formation of the 70S
complex, inhibitingmRNA to be translated into protein (85). Dexamethasone is a
potent synthetic member of the glucocorticoid class of steroid drugs used to
reduce the inflammation and relieve the symptoms of the inflammatory eye (86).
The combination of tobramycin/dexamethasone might be an interesting solution
for dry eye problems caused by inflammation and infection. Lately Alcon is
evaluatinga reformulationof
TobraDex
decreasing theamount of the steroid(from
0.1% to 0.05%) adding an inactive agent (xanthan gum), to stabilize the
combinationandtodelivermoreof eachdrug to theeye. Thecompositionprovides
longer ocular retention for enhanced ocular bioavailability of tobramycin and
dexamethasone and improved suspension of dexamethasone (87). Alcon executed
Phase III clinical trials (ClinicalTrials.gov Identifier: NCT00576251) in June 2007
for
TobraDex
ophthalmic suspension, containing 0.3% of tobramycin and 0.05%
andnowismarketing theproduct asanantibiotic to treatbacterial infections.
SYL1001
The Spanish biotechnology company Sylentis is developing the compound
SYL1001, which is decreasing the pain related to dry eye disease, is acting by
targeting the TRPV1gene expression on the ocular surface (interference RNA,
RNAi) (84, 85). This is an interesting approach as gene silencing is an attractive
aspect avoiding the activity of some proteins by inhibiting its synthesis. In
November 2010Sylentis startedaPhase II safety/efficacy study (ClinicalTrials.gov
Identifier: NCT01776658) on patients with common mild to moderate dry eye
symptoms and persistent daily symptoms formore than threemonths. The study
is still ongoingbut the initial resultsareverypromising.
R932348
Rigel Pharmaceuticals is working on R932348 2,4-‐pyrimidinediamine, a
small JAK3 molecule inhibitor, as a possible treatment for autoimmune diseases
(Figure 16) (88). During trials itwas observed that systemic levels of IL-‐17, IL-‐22,
IL-‐23, and TNF-‐
α
were significantly lower inmice receiving the compound, and T
