Phase 1 Clinical Study of an Embryonic Stem Cell-derived Retinal Pigment Epithelium Patch in Age-related Macular Degeneration

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2018 Mar 20

PMID 29553577

Citations 314

Authors

Lyndon da Cruz

Kate Fynes

Odysseas Georgiadis

Julie Kerby

Yvonne H Luo

Ahmad Ahmado

Amanda Vernon

Julie T Daniels

Britta Nommiste

Shazeen M Hasan

Sakina B Gooljar

Amanda-Jayne F Carr

Anthony Vugler

Conor M Ramsden

Magda Bictash

Mike Fenster

Juliette Steer

Tricia Harbinson

Anna Wilbrey

Adnan Tufail

Gang Feng

Mark Whitlock

Anthony G Robson

Graham E Holder

Mandeep S Sagoo

Peter T Loudon

Paul Whiting

Peter J Coffey

Affiliations

Soon will be listed here.

Abstract

Age-related macular degeneration (AMD) remains a major cause of blindness, with dysfunction and loss of retinal pigment epithelium (RPE) central to disease progression. We engineered an RPE patch comprising a fully differentiated, human embryonic stem cell (hESC)-derived RPE monolayer on a coated, synthetic basement membrane. We delivered the patch, using a purpose-designed microsurgical tool, into the subretinal space of one eye in each of two patients with severe exudative AMD. Primary endpoints were incidence and severity of adverse events and proportion of subjects with improved best-corrected visual acuity of 15 letters or more. We report successful delivery and survival of the RPE patch by biomicroscopy and optical coherence tomography, and a visual acuity gain of 29 and 21 letters in the two patients, respectively, over 12 months. Only local immunosuppression was used long-term. We also present the preclinical surgical, cell safety and tumorigenicity studies leading to trial approval. This work supports the feasibility and safety of hESC-RPE patch transplantation as a regenerative strategy for AMD.

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