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HomemistoryLooking to Cure Retinal Disease

Looking to Cure Retinal Disease

Ground breaking international research into embryonic stem cell therapies could one day deliver the cure for diseases of the retina. With clinical trials now underway in the U.S., Australian sufferers of retinal disease could see a brighter future.

Embryonic stem cell therapies could unlock treatments to many diseases affecting the human race. While scientists have, for many years, experimented with embryonic stem cells, adult stem cells and tissue specific stem cells, few, if any, have made it to clinical trials for human use. However this is now beginning to change and eye diseases will be the first to benefit.

In a medical and legal breakthrough, the second ever clinical trial using embryonic stem cell therapy has been given the green light in the U.S. This trial will examine the safety of a treatment for Stargardt’s Macular Degeneration, a juvenile eye disease which affects one in 10,000 young people in the US.

Macular degeneration is viewed as one of the most likely diseases that can be positively impacted by stem cell therapy. That’s because the cells that need replacing are very accessible for delivering treatments and monitoring effects. In addition, the eye is an immune privileged site, which means injections will not cause an immune response. Furthermore, post treatment, objective tests enable visual acuity to be tested with a high level of accuracy.

This marks the first step towards the development of a transplant ready retina to treat eye disorders

Clinical Trial Gets Green Light

In November 2010, one year after filing an Investigation New Drug Application, the Massachusetts-based company Advanced Cell Technology (ACT) received approval to begin clinical trials on a treatment for patients with Stargardt’s Macular Dystrophy.

According to Professor Bryce Vissel, Head of Research into Regeneration and Neural Plasticity at Sydney’s Garvan Institute, ACT cells have orphan drug status. “This is a special status given to therapies for treatment of diseases that are devastating and/or rare. It is important as it encourages companies and people to develop drugs for diseases that would otherwise not occur. Because orphan status is easier to obtain, companies like to start there and expand. The first trials are key – if a therapy passes safety trials, even on orphan status, they can be trialled more quickly in other diseases that don’t have orphan status,” he said.

ACT’s trials will examine the safety of a therapy the company has developed and tested in a rat model. In the rat model, the group showed that the treatment could extensively rescue photoreceptors, thereby improving vision.

Dr. Robert Lanza, M.D., Chief Scientific Officer at Advanced Cell Technology, said “Our research clearly shows that stem cell-derived retinal cells can rescue visual function in animals that otherwise would go blind. We are hopeful that the cells will be similarly efficacious in patients.”

Approval of ACT’s clinical trial was delayed due to concerns the Federal Drugs Administration held over safety. The FDA issues centred on fears that embryonic stem cells could persist through the culture process, therefore, endangering the patient following transplantation. The FDA also raised concerns about the possibility of patients developing tumours and other biodistribution occurring over the life of a patient.

However Dr. Lanza said “We can detect a single stem cell in over a million Retinal Pigmented Epithelium (RPE) cells. This is especially significant considering the small number of cells (50,000 to 200,000) to be administered into a controlled space in the eye. Stem cells can’t persists in our culture process, and therefore, do not pose a risk of contamination of the final RPE cells to be transplanted.”

Neither is the risk of tumour or long term health safety an issue according to the company, which claims that “implanted RPE cells survived long term in the eyes of animals and no tumours formed as a consequence to the implanted cells.”

Although Stargardt’s Macular Dystrophy affects children from the age of six, the trial will begin with 12 patients aged over 18 years. Each will receive injections of the extremely pure concoctions of human embryonic stem cells directly into the eye. These new healthy cells will replace diseased RPE cells.

Just one other trial for a human embryonic stem cell-based therapy is currently underway in the U.S. Developed by Geron, a stem cell company based in California, the treatment for spinal cord injury first gained approval in January 2009, but was temporarily stopped due to safety concerns. Having been cleared during 2010, the first patient received treatment in October.

Dr. Lanza anticipates that ACT’s macular degeneration trial will be significantly more straightforward than the spinal cord injury treatment being trialled by Geron. “The advantage, of course, is that we’re talking about a very small number of cells going into a very local area.” Using instruments that can track a single retinal cell in the eye in real time, the researchers will be able to see the cells taking up residence in the retina and easily monitor patients’ progress. And, it will be possible to continuously check the vision of the patients to monitor improvements.

ACT’s Chairman and CEO, William M. Caldwell IV said “I think future generations will look back at this time as one of the most exciting in the history of medicine. With this clinical trial and Geron’s, the field of regenerative medicine is poised to take embryonic stem cell therapies from the realm of nebulous potential to that of tangible treatments that will make a difference to millions of people.”

Advancing on Age Related AMD

With clinical trails now approved and underway for a treatment for Stargardts disease, ACT is quickly advancing on a treatment that may positively impact a much larger number of patients.

On 30 November 2010, the company announced that it had filed an Investigational New Drug (IND) Application with the FDA to initiate a Phase I/II multicenter study using human embryonic stem cell derived retinal pigment epithelial (RPE) cells to treat patients with Dry Age-Related Macular Degeneration (Dry AMD). Dry AMD reportedly afflicts more than 30 million people worldwide.

The Phase I/II trial will be a prospective, open-label study designed to determine the safety and tolerability of the RPE cells following sub-retinal transplantation to patients with Dry AMD. A total of 12 patients will be enrolled in the study at multiple clinical sites.

“We can generate a virtually unlimited supply of healthy RPE cells,” said Dr. Lanza. “In our animal studies, we observed significant improvement in visual performance over untreated animals, and did not find any adverse effects of the injection of RPE cells. In extending our studies to human patients, it is our hope that we will show that the injected RPE cells will rescue photoreceptors and slow – if not stop, the progression of macular degeneration.

“We are seeing the beginning of a new era in medical treatment,” he continued. “The hope that stem cell therapies may one day repair and regenerate diseased organs and tissue, goes far beyond what can be accomplished with traditional medicine. This approval shows an apparent readiness by the FDA to work with researchers to move exciting new stem cell based therapies out of the lab and into the clinic.”

Retina Created

A study at the Reeve-Irvine Research Centre and Sue and Bill Gross Stem Cell Research Centre at the University of California, indicates that embryonic stem cells may be capable of regenerating the retina. Research leader, Professor Hans Keirstead and his team have created an eight layer, early stage retina from human embryonic cells, the first 3D structure to be made from stem cells.

Prof. Keirstead claims this is the first step towards developing a transplant-ready retina to treat eye disorders, such as retinas pigmentosa and macular degeneration: “We have made a complex structure consisting of many cell types. This is a major advance to treat retinal disease.”

Prof. Keirstead’s team is credited with originating a method known as differentiation – in which human embryonic stem cells can be directed to become specific cell types. While the method was initially developed for studies on spinal cord injury, his team used the technique to create the multiple cell types necessary for the retina.

Prof. Keirstead said the greatest challenge was in the engineering as the researchers needed to build microscopic gradients for solutions in which to bathe the stem cells to initiate specific differentiation paths.

“Creating this complex tissue is a first for the stem cell field,” he said. “Dr. Gabriel Nistor in our group addressed a really interesting scientific problem with an engineering solution, showing that gradient of solutions can create complex stem cell based issues. What is so exciting with our discovery is that creating transplantable retinas from stem cells could help millions of people, and we are well on the way.”

Now the UCI researchers are testing the early stage retinas in animal models to determine the extent of vision improvement. Positive results will lead to human clinical trials, although these are still likely to be some way off. Prof. Keirstead will not only need to prove the efficacy but also the safety of the trials.

Prof. Vissel says the work is extremely promising. “Hans is working more on a theoretical platform to show that cells can make all the cells needed for the retina. This is very early stage work and not as advanced for the clinic. At the moment, I would say that the implications are much more important as an indication of what these cells can do as opposed to developing a practical therapy. However, I hope this signals a chance for a future of eye repair.”

Bulk Embryonic Stem Cells

Along with legal restrictions on the use of embryonic stem cells, research in this area of science has been hampered by the availability of stem cells. However, a medical breakthrough in Israel in 2010 could provide stem cell researchers with the high quantities of human-derived stem cells needed to treat disorders such as Parkinson’s Disease, diabetes, and age-related macular degeneration.”5

The research project is being conducted at Hadassah University Medical Centre, and lead by Professor Benjamin Reubinoff, director of the Hadassah Human Embryonic Stem Cells Research Centre. Prof. Reubinoff says that his centre has discovered a method to create the optimal conditions in which embryonic stem cells can grow while floating in a medium. Importantly, the method prevents the cells from differentiating into specific, undesirable cell types, which can be dangerous. Until now, stem cells had to be grown on a substrate – an extremely labour intensive process, which limits the number of cells developed through cultivation.

Prof. Reubinoff said “In our research, we took a five day old IVF embryo, with permission, the stem cells multiplied and gave rise to many cultures.

“We show that under specific conditions, you can divide and grow the cells in suspension, opening the window for the development of systems that will allow the large scale development of bulk cultures of stem cells needed for patients.”

Back Home

While in Australia, researchers are more focussed on corneal therapies, the embryonic stem cell therapies being trialled in the United States could lead to benefits for Australians who suffer retinal disease. Associate Professor Di Giralamo, Director of Ocular Research at the School of Medical Sciences, UNSW, said: “Often, when exciting clinical trials happen in the United States, scientists link up with other countries to conduct multi-centre or multi national studies. If this were to happen, it could lead to Australian patients being involved in treatments sooner.”


  1. news.bbc.co.uk/go/pr/fr/-/2/hi/health/6120664.stm
  2. Science Daily October 21, 2009
  3. Advanced Cell.com
  4. Retina Created from Human Embryonic Stem Cells, Science Daily May 27, 2010
  5. http://www.israel21c.org/201005067926/health/moving-closer-to-stem-cell-therapy

What are Stem Cells?

The body’s organs and tissues comprise specialised cells that originate from a pool of stem cells in very early embryo. Throughout life, these cells continuously multiply to repair organs and tissues that are damaged every day.

Scientists have observed stem cells’ ability to divide and renew themselves over with interest over several decades. Importantly, they have discovered that under specific circumstances, cells can be differentiated – or cultivated – into specialised cells that perform specific functions within the body.

The ability to cultivate cells in this way has enabled scientists to observe and obtain a greater understanding of the way in which the body’s tissues and organs regenerate. Armed with this knowledge, they can begin to look at what goes wrong during disease and injury, and ultimately understand how these conditions might be treated and even prevented.

While there are many types of stem cells, some are more valuable to research than others. Tissue specific cells are found in a particular organ or tissue in the body and generate mature cell types within that organ or tissue.

Embryonic stem cells exist only at the earliest stage of development and are capable of generating all cells in the body. They are referred to as pluripotent cells and they are of enormous value to scientific research.

Mouse embryonic stem cells were first isolated in 1981 and are most widely studied. As a result, researchers have discovered many genes associated with different diseases, modelled human diseases and tested treatments in animal models.

Human embryonic stem cells were isolated in 1998 and while they have been found to be more difficult to work with than mouse stem cells, researchers have made remarkable progress.

Recently, scientists have engineered induced pluripotent stem cells (iPS cells) from specialised cells, such as adult skin cells, that offer properties similar to embryonic stem cells.

Human induced pluripotent stem (iPS) cells offer the potential to generate a non-controversial source of patient-specific stem cells without the need to destroy embryos. However, current iPS cells suffer from major drawbacks that may cause unpredictable genetic dysfunction and tumour formation.

Why Embryonic Stem Cells?

Researchers are currently investigating the use of adult, foetal and embryonic stem cells as a resource for various specialised cell types such as nerve cells, muscle cells, blood cells and skin cells. Adult stem cells do not require the manipulation or destruction of an embryo, thus they lack the controversy surrounding embryonic stem cell research. However, these cells are limited in their ability to differentiate into different cell types. Embryonic stem cells, while limited in use due to political and ethical debate, can develop into one of over 200 cell types in the body when given the necessary stimulation.1


1. advancedcell.com/our-technology