After demonstrating in rats that they can use human embryonic stem cells (hESCs) to halt the decline in and rescue the retinal function of lab animals that model age-related macular degeneration (AMD), Hadassah University Medical Center researchers believe they can start clinical trials on people in two years.
AMD - the principal cause of vision loss in residents of the Western world over the age of 50 - occurs when pigmented cells of the macula (center of the retina at the back of the eye) break down and die. The painless disease gradually destroys sharp, central vision, which is needed to see objects clearly and for common daily tasks such as reading and driving.
Some 30 million people around the globe and many tens of thousands of Israelis suffer from AMD, and a growing number are unable to function normally.
An article on the research, by Prof. Benjamin Reubinoff, Prof. Eyal Banin and colleagues, has just appeared in the prestigious scientific journal Cell Stem Cell. They developed a unique technology for the creation of retinal pigment cells from human embryonic stem cells.
This technique is based on Vitamin B3 (also called nicotinamide, which has nothing to do with the dangerous nicotine in tobacco) and a protein called Activin A, which promotes the ripening of the stem cells. When the pigment cells were transplanted into the eyes of rats that suffer from loss of sight because of the dysfunction of retinal pigment cells, they succeeded in halting the growing structural damage to the retina. This part of the eye is the "screen" on which images are displayed and translated into vision by the retina's photoreceptor cells.
A layer of the the pigmented cells is located adjacent to the photoreceptors that absorb and react to the stimulation of light; this layer is sandwiched between the tiny blood vessels that nourish the retina and the photoreceptors. The pigmented cells provide vital support to the retinal photoreceptors; their degeneration and death are the main causes of the development of retinal degeneration, vision loss and age-related blindness, Reubinoff explained to The Jerusalem Post on Monday.
Reubinoff is the director of Hadassah's Human Embryonic Stem Cell Research Center at the Goldyne Savad Institute of Gene Therapy, while Banin is director of the Center for Retinal and Macular Degeneration in Hadassah's ophthalmology department. They are transferring their technology to CellCure Neurosciences Ltd., a company established on the Ein Kerem campus, through Hadasit, the Hadassah technology transfer arm; Reubinoff is CellCure's chief scientific officer.
Two years ago, scientists at Moorfields Eye Hospital and the University of Sheffield in the UK launched an effort to implant hESCs in eyes to treat AMD as part of the London Project to Cure AMD. Reubinoff said the British group was "also aiming at the same target. However, we have succeeded in going farther, as their publications are based on spontaneous differentiation of hESCs, while we describe a novel process in which we can direct their differentiation into functional retinal pigmented cells in a controlled and reproducible process. Spontaneous production is uncontrolled.
"This is to our advantage, as we don't have to rely on a spontaneous process. We did it successfully in three stem cell lines. If one is contemplating movement towards clinical applications, reproducibility is very important."
Reubinoff, one of the pioneers in world hESC research, explained that "the retina is so suitable for implantation because of its accessibility. It is relatively easy to transplant cells into the retina, as it is a confined tissue, and cells will not migrate away. In addition, the eye can be monitored by direct observation, and there are very accurate means of measuring a therapeutic effect in eyes."
"Our findings are an important step towards the use of hESCs for implanting for the renewal of degenerating pigment cells in AMD patients," added Banin.
Today, there is no treatment to arrest the degeneration of the pigmented cells. "All AMD patients start with the 'dry type.' Eight percent of all adults over the age of 75 will eventually become legally blind. One in 10 AMD patients will develop the complication of neovascularization - called 'wet form' AMD - in which the blood vessels hemorrhage.
"Today, there is no cure or way to halt the dry form, and the only way to
prevent the wet form is by injecting the eye with a drug called anti-VEGF factor," said Reubinoff.
While there is always a risk of hESCs causing the uncontrolled cell division, and thus tumors, Reubinoff noted that there were ways of further purifying them into relatively homogeneous, mature cells.
"In all our studies, we did not see any complications, including tumors," he said.
Reubinoff and other Hadassah colleagues made headlines last year when they and Hadasit announced that they had demonstrated for the first time that transplanted neural cells derived from hESCs can reduce the clinical symptoms in animals with a form of multiple sclerosis.