The First Stem Cell Clinical Trial for Wet Macular Degeneration Is Underway in London

Please note: This is an older post and there have been setbacks and significant changes in stem cell research for eye disease since this was first published. For more current information, see Our Readers Want to Know: What Is the Progress of Stem Cell Research for Eye Disease? Answer: It Has a Very Long Way to Go. Also see the author’s updates in the comment section below.

retina with wet AMD

A pioneering clinical trial of a new treatment derived from embryonic stem cells for people with wet age-related macular degeneration (AMD) has been initiated at Moorfields Eye Hospital in London, following a successful operation on a 60-year-old woman. She is the first of 10 persons with wet AMD who will receive the stem cell treatment as part of an 18-month clinical trial to test the safety and effectiveness of this procedure.

In the United States, Ocata Therapeutics has revealed positive results from its small (18-patient) early-stage clinical trials of human embryonic stem cells (hESC) for the treatment of dry age-related macular degeneration and Stargardt disease.

Nevertheless, despite these encouraging – although admittedly very early – results, a clinical trial for stem cell treatment of wet AMD has remained elusive – until now.

 London Project to Cure Blindness logo

This initial operation is a key component of the London Project to Cure Blindness, which was established ten years ago with the goal of curing vision loss in persons with wet AMD. The Project is the result of a partnership that includes Moorfields Hospital, the University College London (UCL) Institute of Ophthalmology, the National Institute for Health Research, and Pfizer Inc..

The London Project to Cure Blindness

Excerpted from About Us at the London Project to Cure Blindness website:

The London Project to Cure Blindness has, for the past 10 years, been developing cell-based treatments to cure blindness associated with age-related macular degeneration (AMD). The group has been culturing embryonic stem cells, which give rise to all human cell types, to grow patches of retinal cells for transplant.

The project aims to bring stem cell therapy for retinal diseases, especially for AMD, to the clinic as rapidly as possible. We believe stem cell-based therapies for these conditions have the greatest chances of preventing blindness, restoring sight, and improving quality of life in the future.

The stem cell approach aims to replace cells in the eye that are either damaged or missing. In AMD the main cells that are initially affected are the retinal pigment epithelium cells (RPE). In the first of the trials developed by the London Project, we are using human embryonic stem cells (hES) that have been transformed into RPE cells. These RPE cells will then be transplanted under the patient’s retina on a specially engineered patch that the London Project has developed.

[Editor’s note: Retinal pigment epithelium (RPE) cells are the deepest cells of the retina. The RPE helps to maintain the health of the retinal photoreceptor cells, called rods and cones. These photoreceptor cells are triggered by light to set off a series of electrical and chemical reactions that helps brain to interpret what the eye sees. The degeneration of the RPE cells also leads to the death of the rods and cones and, ultimately, vision.]

More recently, The London Project has secured funding to examine the use of induced pluripotent stem cell (iPSC) technology for transplantation. This allows the original cells to be taken from the person with the disease themselves and not from another source, such as an embryo.

[Editor’s note: Pluripotent refers to a stem cell that has the power to develop into any type of bodily cell or tissue (“pluri” = many; “potent” = having power). An induced pluripotent stem cell (iPSC) is a type of pluripotent stem cell that can be generated directly from adult cells.]

Another important arm of the project is to develop the technology by which stem cells can be transformed into photoreceptors (primarily cones and rods) and transplanted into patients. It is believed that the photoreceptors are lost after the RPE cells have degenerated.

This first clinical trial, which has been granted permission by the UK regulatory authority, will be for severe wet degeneration, and if successful, will then be also used in dry macular degeneration.

More about Age-Related Macular Degeneration (AMD)

NEI image of how someone with macular degeneration sees: overall blurriness with a blind spot in the center
What a person with AMD sees

Age-related macular degeneration (AMD) is gradual, progressive, painless deterioration of the macula, the small sensitive area in the center of the retina that provides clear central vision. The fovea is located in the center of the macula and provides the sharpest detail vision.

Damage to the macula impairs the central (or “detail”) vision that helps with essential everyday activities such as reading, preparing meals, playing card and board games, and needlework and sewing.

AMD is the leading cause of vision loss for people aged 60 and older in the United States. According to the American Academy of Ophthalmology, 10-15 million individuals have AMD; approximately 10% of people who are affected have the “wet” type of AMD. For more information about vision loss from AMD, see How Does AMD Affect Vision? by Lylas G. Mogk, M.D.

Wet Macular Degeneration

In wet, or exudative, AMD, the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal new blood vessels that develop into a cluster under the macula, called choroidal neovascularization (neo = new; vascular = blood vessels).

The macula is the part of the retina that provides the clearest central vision. Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid under the macula, causing it to lift up and pull away from its base. This damages the fragile photoreceptor cells, which sense and receive light, resulting in a rapid and severe loss of central vision.

In wet AMD, abnormal blood vessels develop under the macula and break, bleed, and leak fluid. This damages the macula and, if left untreated, can result in rapid and severe loss of central vision. The most effective treatments to date for wet AMD are several “anti-angiogenic” drugs.

Angiogenesis is a term used to describe the growth of new blood vessels and plays a crucial role in the normal development of body organs and tissue. Sometimes, however, excessive and abnormal blood vessel development can occur in diseases such as cancer (tumor growth) and AMD (retinal and macular bleeding).

Substances that stop the growth of these excessive blood vessels are called anti-angiogenic (anti = against; angio = vessel; genic = development), and anti-neovascular (anti = against; neo = new; vascular = blood vessels).

The focus of current anti-angiogenic drug treatments for wet AMD is to reduce the level of a particular protein called vascular endothelial growth factor, or VEGF, that stimulates abnormal blood vessel growth in the retina and macula; thus, these drugs are classified as anti-VEGF treatments.

Lucentis, Avastin, and Eylea

At present, these drugs are administered by injection directly into the eye after the surface has been numbed. The needle is very small and is inserted near the corner of the eye — not the center. During the injection procedure, the doctor will ask the patient to look in the opposite direction to expose the injection site, which also allows the patient to avoid seeing the needle. Anti-angiogenic drugs currently in use include Lucentis, Avastin, and Eylea.

More about the Stem Cell Clinical Trial

The ongoing clinical trial at Moorfields Eye Hospital in London is investigating the safety and effectiveness of transplanting RPE cells derived from stem cells to treat people with sudden severe visual loss from wet AMD. These cells are used to replace those at the back of the eye that are diseased in AMD. This is done using a specially engineered patch inserted behind the retina in an operation lasting one to two hours.

In total, the trial will recruit 10 patients over a period of 18 months. Each patient will be followed for a year to assess the safety and stability of the cells and the degree to which their vision is restored.

The first surgery was performed in August 2015 and there have been no reported complications to date. The surgical team hopes to determine the outcome of this first surgery, in terms of initial visual recovery, by early December 2015.

VisionAware will continue to report the results of this clinical trial as they become available.

Additional Stem Cell Information from VisionAware