Nobel laureate says stem cell research is leading to breakthrough treatments

Stem cell research can help to stop macular degeneration and may benefit Parkinson's sufferers, John Gurdon tells Jeanette Wang

PUBLISHED : Monday, 23 December, 2013, 10:15am
UPDATED : Wednesday, 01 January, 2014, 6:37pm

About four years ago, Massimo Sfriso started acting out of character - he kept bumping into people while queuing and failed to react when people tried to shake his hand. Three years ago, he quit driving. Now, aged 55, he walks much more slowly than his peers, avoids crowds and has to pay extra attention when crossing roads.

Eyes are not only the windows to the soul, but also our windows on the world. Sfriso's world has been growing smaller over the years due to two common age-related eye problems, glaucoma and macular degeneration.

The egg has secrets which we don't understand and which could be very useful
professor john gurdon

Two years ago, he lost the central vision in his left eye and now relies on his right eye to read and write. Glaucoma has narrowed his peripheral vision significantly in the past few years, he says, leading to his unusual behaviour. "I started wearing glasses when I was about 10 years old, and I have been changing lenses as often as people change suits," says Sfriso, who had cataract surgery on both eyes in 2006.

"Going to the oculist has become a routine, almost with the same frequency that people go to the cinema, but with much less enjoyment."

Clinging on to a sliver of hope of a cure for his condition in his lifetime, Sfriso was immediately buoyed by a story in the South China Morning Post two Saturdays ago about a stem cell replacement therapy for macular degeneration that may be available as a therapeutic treatment in six months' time.

The article was based on an interview with developmental biologist and Nobel laureate Professor John Gurdon, who says stem cell replacement therapy for the dry form of macular degeneration has been shown to "work quite well" in animals and is now being tested on humans.

"My understanding is that the permission to offer this as a therapeutic treatment is about six months away," says Gurdon, 80, who was the keynote speaker at the University of Hong Kong's recent Frontiers in Biomedical Research symposium.

"The trials in humans take about three months to see if they are successful, and then after that it should really be no problem in making [the treatment] available to patients."

Sfriso says he was delighted by the news. "My doctor always encouraged me by saying that I would see the benefit of medical research in my lifetime. I was astonished to read [Gurdon's] estimate of six months."

Douglas Sipp, head of the science policy and ethics studies unit at Japan's Riken Centre for Developmental Biology, says it is possible that permission to initiate a clinical trial using this treatment may be six months away, but offering the therapy to the masses may take some time since phase II and III clinical trials would take years.

Age-related macular degeneration gradually destroys the sharp, central vision needed for seeing objects clearly and for common tasks such as reading and driving.

It progresses with the death of retinal pigment epithelium (RPE), a dark layer of cells which nourishes the visual cells in the retina. It is the leading cause of visual impairment and blindness in people aged 55 and over in the developed world.

The disease has two forms: wet and dry. Wet macular degeneration represents an advanced stage of the disease, and is almost always preceded by the dry version. It progresses more quickly and can lead to blindness in three months.

Gurdon explains it is now possible to grow in the laboratory layers of stem-cell-derived replacement RPE cells in a sheet, which are then inserted into the eye underneath the retina to support the photoreceptors.

Implantation, he says, is an outpatient procedure with an estimated cost of about £4,000 (HK$50,800). "This would be most likely the first case where these reprogrammed cells are likely to be actually useful to patients."

In July, the Riken centre announced a pilot study to assess the safety and feasibility of transplanting stem-cell-derived RPE cell sheets in patients with wet macular degeneration.

Biotechnology company Advanced Cell Technology (ACT), has been recruiting subjects for phase I and II clinical trials in the United States and Europe since July 2011 to test the safety and tolerability of stem-cell-derived RPE cells in patients with dry macular degeneration at the end of 12 months.

Despite the progressive nature of the eye condition, the vision of ACT's first two subjects appears to have made persistent gains in visual acuity, according to ACT's chief scientific officer Dr Robert Lanza.

The discovery that mature, specialised cells can be reprogrammed to become immature cells capable of developing into all body tissues stems from research that Gurdon conducted as an Oxford postgraduate student in 1958.

At that time, he proved - contrary to the conventional wisdom of the day - that every cell in the body contains the same genes.

He had taken a cell from an adult frog's intestine, removed its genes and implanted them into an egg cell, which grew into a clone of the adult frog. This discovery - which won him the Nobel Prize in Physiology or Medicine last year - was confirmed by other scientists and initiated intense research and further development of the technique.

It eventually led to the cloning of mammals (including Dolly the sheep) and research into regenerative medicine.

Apart from macular degeneration, the other major area that stem cell researchers are focusing on is neurodegenerative disorders such as Parkinson's disease, says Gurdon.

Researchers are trying to use stem cells to make nerve cells that produce dopamine, the chemical that allows messages to be sent to the parts of the brain that control movement.

Parkinson's disease kills dopamine-producing neurons, causing patients to develop tremors and rigidity, and slowing their movements down. These stem-cell-derived neurons, which have shown benefits in tests on rats,could be an alternative source of new cells for Parkinson's patients.

The other option - which Gurdon says has about a 30 per cent success rate in delaying the onset or progress of the disease - is to use dopamine-producing neurons obtained from human fetuses.

But there is not enough fetal tissue to treat the large number of Parkinson's patients (about 18 fetuses are needed for one implant, Gurdon says), and there are ethical issues.

However, stem cell treatments have their downsides, too. There may be biological risks, including teratoma formation, a type of cancer that occurs when stem cells differentiate into multiple cell types and form incompatible tissues that can include teeth and hair.

For all the potential that regenerative medicine holds, the challenge still remains of how precisely to instruct immature cells to differentiate or specialise in exactly the way needed.

Gurdon is hoping to find a way of obtaining spare heart or brain cells from skin or blood cells. To do this, one has to know the actual mechanism that goes on in the cells when they change from adult back to embryo. "We only know a little bit of how it's done," admits Gurdon.

This is why, in spite of his age, he still works in the Cambridge lab, trying to understand the biochemical basis of cell rejuvenation.

"The egg has a natural way of rejuvenating adult cells. It's the only cell which can do this. When a sperm enters an egg, it is correctly reprogrammed 100 per cent perfectly every time," says Gurdon.

"So the egg has secrets which we don't understand and which could be very useful - that is why we want to know the mechanism of how the egg does these things."