edoc

Tolerability and safety of GS-101 eye drops, an antisense oligonucleotide to insulin receptor substrate-1 : a 'first in man' phase I investigation

Kain, Hermann and Goldblum, David and Geudelin, Bernard and Thorin, Eric and Beglinger, Christoph. (2009) Tolerability and safety of GS-101 eye drops, an antisense oligonucleotide to insulin receptor substrate-1 : a 'first in man' phase I investigation. British journal of clinical pharmacology, Vol. 68. pp. 169-173.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6006737

Downloads: Statistics Overview

Abstract

AIMS: GS-101 (GeneSignal, Epalinges, Switzerland) is an antisense oligonucleotide that inhibits the expression of the scaffold protein insulin receptor substrate-1 (IRS-1). Inhibition of IRS-1 results in the prevention of neovascular growth and was shown to prevent the angiogenic process in preclinical in vitro and in vivo experiments. There is therefore a strong therapeutic rational for targeting angiogenesis in pathological neovascularization. We aimed to investigate the safety, tolerability and bioavailability of GS-101 eye drops. METHODS: This was a Phase I open-label study. The investigation was performed in two steps. Local ocular tolerability was first assessed with the application of one single low dose in one eye. After no signs of intolerance were observed in the subjects, the dose escalation phase of the study was initiated, and the remaining subjects received three times daily escalating doses of GS-101 in one eye for 14 days. RESULTS: The 14 healthy volunteers tolerated well 14 days' continued use of escalating doses of GS-101 from 43 to 430 microg per day. 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. CONCLUSIONS: The tolerability profile obtained from this study suggests that GS-101 is safe for human use. Further clinical evaluations in diseases related to abnormal angiogenesis are being targeted. In particular, the neovascularization-related orphan indications of corneal graft rejection, retinopathy of pre-maturity and neovascular glaucoma are currently under Phase II clinical investigation and are showing promising results.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Gastroenterology (Beglinger)
03 Faculty of Medicine > Bereich Spezialfächer (Klinik) > Ehemalige Einheiten Spezialfächer (Klinik) > Ophthalmologie (Flammer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Spezialfächer (Klinik) > Ehemalige Einheiten Spezialfächer (Klinik) > Ophthalmologie (Flammer)
UniBasel Contributors:Beglinger, Christoph and Goldblum, David
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Blackwell
ISSN:0306-5251
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:01 Feb 2013 08:46
Deposited On:01 Feb 2013 08:45

Repository Staff Only: item control page