Page 163 - 80_01

Dry
eye
disease
compounds…

CIS-­-UROCANIC
ACID

LaurantisPharma
Ltd
and
Kuopio
University
Hospital
are
developing
eye

drops
containing
Cis-­-urocanic
acid
(cis-­-UCA)
as
treatment
for
ocular
surface

inflammation
associated
with
moderate
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

to
cytotoxicity
in
epithelial
cells.
During
tests
it
was
demonstrated
that
is
inhibiting

the
secretion
of
pro-­-inflammatory
cytokines
from
human
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-­-UCA
may

be
a
safer
and
more
effective
alternative
to
current
drugs
used
for
acute
and
long-­-
term
treatment
of
dry
eye.
From
November
2011
to
May
2012
Laurantis
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
the
compound.

THYMOSIN
BETA
4

RegeneRx
Biopharmaceuticals
is
developing
RGN-­-259
which
is
a
0.1%

Thymosin
Beta
4
(Tß4)
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
regeneration
peptide
(53).
In
human

body
is
a
protein
encoded
by
the
TMSB4X
gene
(GenBank
accession
number:

NC_000023.10).
During
preclinical
evaluations
it
was
demonstrated
that
Tß4
is

promoting
corneal
epithelial
intercellular
adhesions
following
injury
in
animal

models
of
dry
eye
(54).
In
June
2011
RegeneRx
started
Phase
II
safety
and
efficacy

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

ocular
discomfort
(55).

159