March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Lentiviral Vector Gene Replacement Therapy in Stargardt Disease and Usher Syndrome type Ib
Author Affiliations & Notes
  • J T. Stout
    Ophthalmology, Casey Eye Institute-OHSU, Portland, Oregon
  • David J. Wilson
    Ophthalmology, Casey Eye Institute-OHSU, Portland, Oregon
  • Richard Weleber
    Ophthalmology, Casey Eye Institute-OHSU, Portland, Oregon
  • Mark Pennesi
    Ophthalmology, Casey Eye Institute-OHSU, Portland, Oregon
  • Maureen Toomey
    Ophthalmology, Casey Eye Institute-OHSU, Portland, Oregon
  • Peter Francis
    Ophthalmology, Casey Eye Institute-OHSU, Portland, Oregon
  • Jose A. Sahel, Jr.
    UMR-S 968, Institut de la Vision, Paris, France
  • Isabelle Audo
    CHNO des Quinze-Vingts, Centre de Recherche Institut de la Vision, Paris, France
  • Saddek Mohand-Said
    CHNO des Quinze-Vingts, Centre de Recherche Institut de la Vision, Paris, France
  • Stuart M. Naylor
    Oxford BioMedica UK Ltd, Oxford, United Kingdom
  • Footnotes
    Commercial Relationships  J. T. Stout, Oxford Biomediuca is sponsoring the clinical trial (F); David J. Wilson, Oxford Biomedica is sponsoring the trial (F); Richard Weleber, Oxford Biomedica is sponsoring the trial (F); Mark Pennesi, Oxford Biomedica is sponsoring the trial (F); Maureen Toomey, Oxford Biomedica is sponsoring the clinical trial (F); Peter Francis, Oxford Biomedica is sponsoring the clinical trial (F); Jose A. Sahel, Jr., Oxford Biomedica is sponsoring the clinical trial (F); Isabelle Audo, Oxford Biomedica is sponsoring the clinical trial (F); Saddek Mohand-Said, Oxford Biomedica is sponsoring the clinical trial (F); Stuart M. Naylor, Employee of Oxford Biomedica (E)
  • Footnotes
    Support  Oxford Biomedica
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1936. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      J T. Stout, David J. Wilson, Richard Weleber, Mark Pennesi, Maureen Toomey, Peter Francis, Jose A. Sahel, Jr., Isabelle Audo, Saddek Mohand-Said, Stuart M. Naylor; Lentiviral Vector Gene Replacement Therapy in Stargardt Disease and Usher Syndrome type Ib. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1936.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: : Single gene disorders are responsible for several conditions that lead to profound vision loss including Stargardt disease and Ushers syndrome. These diseases may be amenable to gene replacement therapy and trials are underway to evaluate safety and efficacy of this therapeutic approach. The purpose of this report is to describe the surgical technique and endpoint determination for lentiviral vectors based on an EIAV-based platform in treating inherited retinal degenerations.

Methods: : Phase I/II trials are designed principally to evaluate the safety and efficacy of gene replacement therapy in patients with Stargardt Disease and Usher Syndrome type 1b. Eligible patients must have disease-causing mutations on both chromosomes, confirmed by segregation analysis, for the gene ABCA4 (Stargardt disease) or MYO7A (Usher 1B). Study design is that of dose escalation to determine safety in an initial cohort followed by efficacy assessment in subsequent cohorts. Lentiviral vectors (EIAV-ABCA4 for Stargardt, EIAV-MYO7A Usher 1b) are administered subretinally following vitrectomy and efficacy endpoints consist of visual acuity, OCT, GATE visual field, multifocal and full field ERG and spacing of the cone mosaic (as assessed with adaptive optics).

Results: : The Stargardt disease trial is underway following FDA and AFSSAPS approval, FDA approval has also been received for the Usher trial. Thus far, subretinal fluid reabsorption has been rapid and complete and without inflammatory consequence.

Conclusions: : No toxicity has been noted in Stargardt disease patients undergoing gene replacement therapy with EIAV-ABCA4 in the first cohort. The lentiviral vector platform has the potential advantage of permanent expression of gene products implicated in retinal disease and in particular those that are too large for other available vectors.

Clinical Trial: : http://www.clinicaltrials.gov NCT01367444

Keywords: gene transfer/gene therapy • retinal degenerations: hereditary 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×