I thought there was a 50/50 chnace that I wouldn’t be around to see this through. It was serious. When we picked up our first cells, we sent bodyguards. (ASSOCIATED PRESS)
Robert Lanza, M.D. (ASSOCIATED PRESS)
Transplanting stem cells removed from human embryos is at the leading edge of medical research by scientists like Hans Keirstead and Robert Lanza. (ASSOCIATED PRESS)
An inherited degenerative disease robbed Ryan Rapoport, 10, of his vision in seven quick months.
But the Seattle fifth-grader now sees hope on the horizon: After several years of scrutiny, the Food and Drug Administration gave the green light to a California biotech company to use human embryonic stem cells as a treatment for the disease that robbed Ryan of his sight.
Only the second company to be approved to use embryonic stem cells in a clinical trial, Santa Monica’s Advanced Cell Technology (ACT) expects to begin testing the treatment as early as February, said the company’s chief scientific officer Dr. Robert Lanza.
“I have felt pretty hopeless,” said Darrin Rapoport, Ryan’s father. “This has literally allowed me to smile again.”
Heralded a decade ago as the savior of all that ails man, embryonic stem cells were supposed to provide cures for everything from spinal-cord injuries to heart disease.
Stem cells, which are abundant in embryos, have the ability to form into any kind of human cell — eyes, livers, intestines — giving hope that scientists could one day “grow” healthy human tissue to replace damaged or diseased organs.
But research into the field was outlawed by the Bush administration, which lumped the work into the cultural debate about abortion.
In 2001, Bush banned all federal funding of research on embryonic stem cells beyond those that used the 21 cell lines in existence at the time, scaring away venture capitalists and limiting what researchers could do.
Many scientists moved on to different areas of research. Some worked with less malleable stem cells from tissues of adults, with mixed results.
In March 2009, President Obama reversed the Bush policy. Now the issue is back in the courts, with embryonic stem-cell researchers expressing cautious optimism that research using those unspecialized cells, mostly harvested from unused embryos from fertility clinics, will begin anew.
At least a dozen scientists in California alone are expected to apply for FDA clinical-trial approval in the next four years for research into treatments for diabetes, Alzheimer’s disease and multiple sclerosis.
But the first two approved clinical studies may be the most amazing — making the paralyzed walk and the blind see.
For safety’s sake, Advanced Cell Technology’s initial trial for sufferers of the disease Ryan suffers from, Stargardt macular dystrophy, will be limited to only 12 patients — all of them adults with an advanced form of the condition.
Using a large needle, doctors involved in the study in Oregon, Massachusetts and New Jersey will inject retinal cells derived from human embryonic stem cells into patients’ eyes.
In rats and mice, this process halted the progressive disease without causing tumors or other side effects.
“These cells have been really performing quite robustly in the animals.
“If we see a fraction of that in a human patient, it’s a home run,” Lanza said.
If the trial proves the process is safe, it could be tested on younger patients to see if it can prevent or reverse blindness. The Rapoports, who have two other sons who have a 25 percent chance of developing the disease, will eagerly be monitoring the results.
“Ryan really wants to do this. He asks me about it on an almost daily basis,” his dad said.
STARGARDT macular dys trophy causes blindness by essentially starving the eye’s photoreceptors to death. Cells called retinal pigment epitheliums nourish the retina and maintain the photoreceptor’s health.
The expectation is that by injecting new RPE cells directly into the eye, scientists can reverse the damage and rescue those photoreceptors.
To prepare the eye and prevent the retina from detaching during the injection of new cells, doctors in the study will first perform a vitrectomy, the removal of some of the clear jelly from the middle of the eye. Then they will make a microscopic hole in the retina to inject the new RPE cells, said Dr. Peter Francis, associate professor at the Casey Eye Institute at Oregon Health and Science Institute, who will be one of the first clinicians to participate in the study.
Depending on the stage of the study, doctors will inject 50,000 to 200,000 RPE cells into patients’ eyes.
Francis said he and other doctors are particularly intrigued by this study because there is currently no treatment for Stargardt’s disease. The degenerative condition causes significant blind spots in a person’s central vision that start out small — spots over letters in books, for example — and grows to the point where some people can’t see whole faces or larger objects.
The hope is that new, healthy RPE will not only stop the disease’s progress, but might even reverse some of that vision loss. If proven safe, the treatment could be applied to a number of other degenerative eye diseases.
“Right now, we’re limited to genetic counseling and low-vision aids,” Francis said.
“We always lived with the hope that we would see this type of treatment.”
One of the benefits of working with the eye is that it is protected from body’s immune system, so injecting foreign cells into the eye will not likely cause the body to reject the treatment.
Another benefit is that the eye is a window to the, well, the eye.
“You can just look into the eye and see individual retinal cells. If anything started to grow, we could see it in real time,” Lanza said.
For the last decade, researchers have been grafting adult stem cells taken from the limbus of a patient’s own eye to treat corneal blindness. Unlike those limbal cells, embryonic stem cells have the ability to become any kind of new, healthy cell, in this case RPE.
The main concern of regulators and doctors monitoring this study is that the very malleability that embryonic stem cells are prized for also make them potentially dangerous.
The cells scientists will inject into patients will be stem cells that have been turned into RPE cells by scientists — but what if a few “undifferentiated,” or unspecialized, cells ended up in the mix?
Regulators need assurance that patients would be protected against unintended growths.
“You don’t want to end up with a tooth growing in your brain,” Lanza said.
The company underwent intense scrutiny to make sure none of the cells in their trials were undifferentiated — or liable to turn into something other than RPE.
“They wanted to make sure there were no icebergs beneath anything,” Lanza said of the FDA.
The company was tasked with proving the purity of their cells — a benchmark they believe other companies searching for FDA approval will have to match.
LANZA started his career in this field in 1999, back when the mere mention of “embryonic stem cells,” invoked images, as he puts it, “of little embryos with arms and legs being pulled apart.”
As political fervor built, he watched colleagues leave the country in search of more hospitable climes.
But he stayed at ACT, working through repeated losses of funding, FBI interventions and death threats.
“I thought there was a 50/50 chance that I wouldn’t be around to see this through. It was serious,” he said. “When I went out walking, I’d be listening for people in the bushes. When we picked up our first cells, we sent bodyguards.”
After the 2008 elections, however, Lanza said the shouts of “Murderer!” come much less frequently. This, he attributes to a greater understanding of what embryonic stem-cell research is.
“My goal is to do something where I can make a difference and help,” he said. “I believe in this, and I knew in the end, that once people are educated, they’d start to understand this is going to help people.”
One of the people who also believed is William Caldwell, now chairman and CEO of ACT. Caldwell and his wife made personal loans to the company to help keep it afloat during some of the early days.
“The company was run by scientists, and in order for them to survive, they had to sell off non-core assets,” Caldwell said.
ACT received a nod from the FDA in November, a few months after the agency gave approval to Menlo Park, Calif.-based Geron Corp. to test embryonic stem-cell treatments on patients with spinal-cord injuries.
Using research that began in 2004, University of California-Irvine scientist Hans Keirstead discovered that, using embryonic stem cells, he was able to restore paralyzed rats’ ability to walk. Geron is now exploring the treatment’s effectiveness on humans in several medical centers across the country.
ACT and other companies watched the Geron application process with great interest, particularly when the FDA placed a clinical hold on Geron’s drug after some of the animals injected with the treatment developed small cysts within their spinal cords.
Geron developed new procedures to minimize the risk, and the FDA lifted its hold.
The legwork by ACT and Geron is expected to pave the way for other companies looking to create similar treatments for debilitating and life-threatening diseases.
ACT recently filed a request to begin trials to test a potential treatment for age-related dry macular degeneration, a chronic eye disease that causes central vision loss by deteriorating a layer of tissue on the inside back of the eyeball.
Associated with the elderly, dry macular degeneration affects 2 million people in the United States.
And in the next few years, the company plans to pursue therapies for making red blood cells and platelets.
The company that once wasn’t sure it could keep its lights on, now feels optimistic about its future — and the future of this new frontier in medicine.
“We’re clearing the path,” Lanza said. “Even if we were to go under now, the field has made it.”