Stem cell based treatment strategy for Age-related Macular Degeneration (AMD)

Lead Research Organisation: University College London
Department Name: Institute of Ophthalmology


Retinal degeneration represents a group of blinding diseases that are increasingly impacting the health and well being of
Californians. It is estimated that by 2020, over 450,000 Californians will suffer from vision loss or blindness due to the age-related
macular degeneration (AMD), the most common cause of retinal degeneration diseases in the elderly. AMD is a progressive
ocular disease of the part of the retina, called the macula, which enables people to read, visualize faces, and drive. The disease
initially causes distortion in central vision, and eventually leads to legal blindness.
A layer of cells at the back of the eye called the retinal pigment epithelium (RPE), provide support, protection, and nutrition to
the light sensitive cells of the retina; the photoreceptors which consist of rods and cones . The dysfunction and/or loss of these
RPE cells play a critical role in the loss of the PR?s and hence the blindness in AMD. Effective treatment could be achieved by
proper replacement of damaged RPE and retinal cells with healthy ones. More specifically, the regenerated and restored RPE
layer would prevent the irreversible loss of the PR?s. However, the lack of a feasible approach to restore the RPE cells has
prevented the realization of a potential therapy.
Recent advances in knowledge and technology of human embryonic stem (hES) cells brings new hope for the development of
cell replacement treatment. hES cells are capable of unlimited self-replication and production of different cell types. RPE cells
derived from hES cells are a potentially unlimited and robust source for regenerating RPE.
We hypothesize that the dysfunction and/or loss of RPE can be overcome by regenerating and restoring the RPE through the
transplantation of functionally polarized RPE monolayers derived from hES cells. Such RPE cells derived from hES can then be
transplanted into the eye, using minimally invasive surgical procedures saving the PR from dying.
Our group is composed of unique multidisciplinary members who collectively have more than two decades of experience in
efforts to restore sight to the blind as well as retinal cell transplantation and stem cell research. Our plan for this grant is to use
our expertise and infrastructure to show to the FDA the success of our preclinical tests using hES derived RPE cells in order to get
approval to conduct a clinical trial in patients at risk of vision loss due to AMD.
Limit Public

Technical Summary

The project objective is to develop a cellular therapy for AMD using retinal pigment epithelium (RPE) derived from human
embryonic stem cells (hESC). AMD is a leading cause of irreversible vision loss, and the late, dry form is associated with RPE loss.
The RPE monolayer is integral for maintenance of healthy photoreceptors (PR), and together with the PR provides the
transducing interface for visual perception. We hypothesize that lost RPE can be restored through transplantation of functionally
polarized RPE cell monolayers derived from hESC.
We have derived RPE from hESC?s and shown disease modifying activity in animal models. Building on these results, we will use
in-vivo imaging and post-mortem histology in our GLP animal trial to show safety (i.e., no infection/retinal detachment rates;
treatable intraocular inflammation). Long-term animal studies will be conducted to exclude tumor formation. Also efficacy (i.e.,
PR and RP function) will be measured by behavioral and/or functional-electrophysiological testing in the rat and pig models.
Agreements are in place to utilize FDA approved hESC (Geron Inc) and cGMP hESC (Shef 1; from our partner P.I.). We will implant
hESC-derived RPE differentiated into a polarized monolayer under cGMP conditions (City of Hope) on FDA-approved cGMP
synthetic substrates. The hESC-derived RPE monolayers will be implanted through the use of well-established minimally
invasive, 45 minute surgical procedure. After implantation of hESC-derived RPE, we will repeat above tests on a monthly interval
allowing us to assess safety and efficacy. GLP animal experiments and histology will be done at Comparative Biosciences, Inc. If
immunosuppression is required, we will implant an FDA approved intraocular steroid delivery platform. With the success of
these GLP preclinical studies along with a comprehensive plan for Phase 1 clinical trial in at risk AMD patients, we will be able to
submit an IND submission that has a very high likelihood of being successfully reviewed by the FDA.


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Description Moorfield's Eye Hospital 
Organisation Moorfields Eye Hospital NHS Foundation Trust
Department NIHR Moorfields Biomedical Research Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution The process for manufacturing the therapeutic and clinical trial were devised by the research team.
Collaborator Contribution In partnership with the BMRC in Ophthalmology based at Moorfield's Eye Hospital, the first clinical trial in the uK of a therapeutic derived from human embryonic stems will go into a Phase I/II clinical trill.
Impact Major output is the clinical trial approval.
Start Year 2010
Description Pfizer 
Organisation Pfizer Ltd
Department Neusentis Pfizer
Country United Kingdom 
Sector Private 
PI Contribution Science, preclinical and clinical
Collaborator Contribution Regulatory and QA
Impact Commercial
Start Year 2009
Title hESC-derived RPE for the treatment of AMD 
Description Human embryonic derived retinal pigmented cells for the treatment of age-related macular degeneration. 
Type Therapeutic Intervention - Cellular and gene therapies
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2013
Development Status Under active development/distribution
Clinical Trial? Yes
Impact First clinical trial in UK of a human embryonic derived therapy. 
Description Charities 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact This project was presented to a number of charities including RNIB and Macular Disease Society.

Was presented in charity newsletters.
Year(s) Of Engagement Activity 2007
Description MRC Parliamentary presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Poster Presentation
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact My presented it work to parliament as part of the MRC's anniversary.

Dissemination of current regenerative medicine platform in the UK.
Year(s) Of Engagement Activity 2012
Description Newsletters 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Open dialogue on stem cell issues

Public engaged in ethics discussion
Year(s) Of Engagement Activity 2010,2011
Description Patient Group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact MDS prsentation

MDS toured facilities
Year(s) Of Engagement Activity 2010,2011,2012