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conference
series
.com
July 17-19, 2017 Chicago, USA
World Congress and Expo on
Optometry & Vision Science
Volume 2, Issue 1 (Suppl)
Optom Open Access, an open access journal
ISSN:2476-2075
World Optometry 2017
July 17-19, 2017
Integrin peptide therapy for treating Vitreoretinal Disorders
R
esearchers have long known that integrins serve as “bridges” between cells and regulate how cells interact with each
other and with the extracellular matrix. There are 27 known integrins, each named for a specific alpha-beta combination.
Integrins have been associated with angiogenesis, inflammation, and thrombosis, so it makes sense to investigate them as
potential treatments for ocular disorders. However, finding agents that can inhibit integrins has been challenging. One integrin
antagonist, lifitegrast (Xiidra, Shire), recently received US Food and Drug Administration approval for the treatment of dry
eye. ALG-1001 (Luminate, Allegro Ophthalmics) has the potential to target four different integrin sites. This agent has two
mechanisms of action. First, it inhibits three integrins considered to be angiogenic; angiogenesis is a key factor in AMD, DME,
and RVO. Integrins are known to work both upstream and downstream of the VEGF pathway. Second, ALG-1001 inhibits an
integrin-mediated pathway of the vitreoretinal interface, making it capable of inducing posterior vitreous detachment (PVD).
Anti-edematous Effect:
ALG-1001 seems to have clear anti-edematous and antiproliferative effects. Its mechanism is quite
different from that of anti-VEGF agents; therefore, this compound has potential as both adjunctive and standalone therapy. It
addresses the goal of using multiple therapeutic approaches with different mechanisms of action that target different aspects of
disease. Because ALG-1001 inhibits multiple integrins, including αvβ3, αvβ5, and α5β1, it may be able to prevent new blood
vessel formation while concurrently stopping leakage from existing blood vessels. Early study results have suggested that this
combination of integrin inhibition may be potent enough to be used as monotherapy for DME and AMD. What is particularly
interesting, however, is that these early data also suggest that anti-integrin therapy may be effective for patients who have not
been successfully managed with anti-VEGF treatments alone. A phase 1 study of ALG-1001 in DME enrolled 15 patients with
poor vision and substantial intraretinal fluid who had undergone more than 10 anti-VEGF injections. In this trial, eight of the
15 (53%) patients improved by 3 to 5 lines in visual acuity testing; four (50%) of these patients improved from legal blindness
to functional vision in the range of 20/40 to 20/60. Additionally, more than half the patients in this phase 1 trial experienced a
30% to 80% reduction in central macular thickness. The substantial improvement seen in these patients has driven the ongoing
investigation of ALG-1001 for treatment of DME.
Vitreolysis Effect:
Vitreomacular traction (VMT) is a pathology associated with the vitreoretinal interface. In a normally
aging eye, the vitreoretinal interface gradually releases. In eyes with VMT, although the rest of the vitreous is released from the
retina, a residual area of adhesion remains. It is extremely difficult to effect that release without causing damage to the retina.
From a pharmacologic standpoint, it has recently become possible to use an enzyme to achieve vitreomacular detachment,
although surgical removal of the adhesion remains the standard of care. Inducing a posterior vitreous detachment (PVD) in
a patient with a normal vitreoretinal interface can be viewed as assisting part of the spectrum of normal vitreous aging. There
are numerous hypotheses about how the vitreous releases, and some suggest that overstimulating VEGF could create a depot
of sorts at the vitreoretinal interface, possibly causing disease to progress. There is a significant body of evidence that suggests
that inducing a PVD may inhibit the progression of retinal disease, particularly DR. We know that, in proliferative DR (PDR),
blood vessels grow onto the vitreous scaffolding. But if the vitreous has undergone a PVD and elevated itself, there would
be no scaffolding for vessels to grow onto. In theory, this could stop the proliferation from occurring. Or it might cause the
growth to behave more like coral branching out from the seabed, doing little damage because it is not causing traction. In the
phase 1 study of ALG-1001 in DME, researchers noted a high rate of PVD. Evidence suggests that ALG-1001 inhibits a fourth
Hugo Quiroz-Mercado
University of Colorado, Mexico
Hugo Quiroz-Mercado, Optom Open Access 2017, 2:1 (Suppl)
DOI: 10.4172/2476-2075-C1-001