Gene Signal and Collaborators Publish GS-101 Clinical Data Suggesting Safe and Effective Inhibition of Abnormal Ophthalmic Blood Vessel Growth

Data Published in Ophthalmology Show GS-101 May Prevent Corneal Graft Rejection


The British Journal of Clinical Pharmacology (BJPC) publishes a new study demonstrating that  Gene Signal’s GS-101 eye drops are safe for human use, at 5 times the therapeutic dose.

The 14 healthy volunteers tolerated well 14 days’ continued use of escalating doses of GS-101 from 43 to 430 micrograms/day (5 times the therapeutic dose of 86 micrograms/day identified by Phase II Study). Other than itching experienced also in the control eye by one subject and determined to be unrelated to the study treatment, no signs of intolerance were observed. GS-101 is an antisense oligonucleotide that inhibits the expression of IRS-1 in pathological angiogenesis.

Dr Herman L. Kein (1), David Goldblum (1), Bernard Geudelin (2), Eric Thorin (3), Christoph Beglinger (4)

1University Eye Clinic in Basel Switzerland , 2Mediante GMBH, Basel Switzerland, 3Centre de Recherche de l'Institut de Cardiologie de Montréal, Montréal, Québec H1T 1C8,Canada, 4University Hospital Basel (Switzerland), Gastroenterology

"Tolerability and safety of GS-101 eye drops, an antisense oligonucleotide to insulin receptor substrate-1: a  first in man  phase I investigation“.
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Dr Salvador Garcia Delpech presents his experience with GS-101 at the French Ophthalmic Society (SFO) meeting. Dr Garcia Delplech explained that while GS-101 regulates angiogenesis, it does not completely suppress VEGF, protecting thus the limbal vasculature.  His presentation won the award for the Best Presentation in the European Symposium of the SFO and is posted on ‘Ocular Surgery News’.

Salvador Garcia-Delpech, MD, University Hospital of Valencia, Spain says:
”GS-101 acts on RNA regulating the production of VEGF, but unlike classical anti-VEGF agents, it does not completely suppress the VEGF”
"The reduction of VEGF is about 50%. This maintains the quantity of VEGF that is necessary to sustain limbal vasculature"


The Journal of Pharmacology and Experimental Therapeutics (JPET) publishes a new study demonstrating the potent in-vivo anti-angiogenic effect of GS-101 antisense oligonucleotide.  

The study shows that GS-101’s anti-angiogenic effect is achieved by preventing the expression of Insulin Receptor Substrate-1 (IRS-1), demonstrating that IRS-1 is directly involved in the angiogenesis process.  The study also shows that GS-101 combines a reduction in the activity of angiogenesis pathway (IRS-1 and VEGF) with an anti-inflammatory action (by suppressing IL-1β).

Salman Al-Mahmood 1*, Sylvie Colin 1, Nada Farhat 2, Eric Thorin 3, Cecile Steverlynck 1, Sylvain Chemtob 4 

1 Gene Signal Company 2 Montreal Heart Institute 3 Université de Montreal, Montreal Heart Institute 4 Université de Montreal / CHU Ste-Justine

Potent in vivo anti-angiogenic effects of GS-101, an antisense oligonucleotide preventing the expression of Insulin Receptor Substrate-1
  


GS-101 eye drops inhibit hem and lymphangiogenesis in a dose dependent manner. Abstract presented at ARVO 2009.


Phase II trials interim results for GS-101 in Neovascularisation associated Corneal Graft Rejection have been announced at Congresses in Europe and N. America ,  September - November 2008. Additional abstract to be presented at ARVO 2009.