Scientists have made stunning progress helping paralyzed rats and mice walk again by injecting them with stem cells. Now researchers at Geron of Menlo Park want to take the next step — in people.
They hope to get federal permission to inject those cells into damaged spinal cords. The procedure — which Geron intends to do next year — would be the first human tests of a treatment derived from human embryonic stem cells, the highly versatile body cells that can be coaxed into becoming almost any tissue in the body.
If the U.S. Food and Drug Administration gives its OK and the injections help, it could bring hope to many of the more than 250,000 people in this country with spinal disabilities.
“We don’t have our hopes sky-high,” said Don Reed of Fremont, whose son Roman Reed was left a quadriplegic after breaking his neck in a college football game 11 years ago. He also hopes the FDA and Geron don’t rush into human tests until all safety concerns are resolved.
But if Geron’s procedure helps patients, “it would be fantastic,” Reed added. “Nobody should go through the hell that paralyzed people have to.”
Nonetheless, the plan has aroused concerns among some stem-cell researchers who claim Geron is moving too fast. They have urged the company to do more tests in non-human animals before trying it in people, because they fear cells could cause tumors or other health problems in those receiving the injections.
“Frankly, I cannot conceive of a human trial with the use of human embryonic stem cells following immediately from experiments in rodents only,” said Jerry Silver, a neuroscience professor and stem-cell researcher at Case Western Reserve University in Cleveland. “Many treatments that work in rodents to alleviate disease fail miserably in humans.”
Stem cells are the body’s basic building blocks and they essentially fall into two major categories: embryonic stem cells, which can grow into any tissue, and adult stem cells, which are more specialized and less flexible.
Treatments derived from adult stem cells already are being used to help people with everything from cancer to various blood disorders. But adult stem cells can be difficult to locate for study, are limited in the body and sometimes develop abnormalities that can hinder their medical usefulness.
Working with embryonic stem cells, first isolated in 1998, can pose problems, too. For one thing, they are highly controversial because the only way to obtain them for research is to destroy an embryo. As a result, President Bush in 2001 severely limited federal money for studies involving human embryonic stem cells.
But because those cells are so versatile and easy to grow in large numbers in laboratories, they can be turned into treatments more easily and at less cost than is the case with adult stem cells, many scientists maintain. And given what has been learned from tests of human embryonic stem cells in rodents with spinal cord injuries, Geron executives believe it is time to see if the cells can be used on people, too.
Spinal cord injuries frequently damage one part of nerve cells called axons, the long wire-like extensions of the nerve cells. That damage disrupts the Axon’s ability to transmit information, resulting in paralysis.
For its test, Geron proposes to turn human embryonic stem cells into the precursors for specialized nerve cells, called Oligodendrocyte progenitor cells. Surgeons then would inject the cells into the spinal injury with the help of a special stabilizing frame the company has developed.
If everything goes as planned, the progenitor cells would help form new axons and also turn into oligodendrocytes, which help form an insulating sheath for the axons, called Myelin.
The test probably would involve a few dozen patients, all of whom would have irreversible spinal injuries. Initially, the idea would be to merely determine if the injections were safe. But Geron executives hope additional tests would demonstrate the procedure’s effectiveness in repairing damaged axons and restoring Motor function in less severely injured people.
Geron has been collaborating with researchers at the University of California-Irvine, who reported in October last year that paralyzed rats could walk nine weeks after being injected with oligodendrocyte progenitor cells derived from human embryonic stem cells.
The FDA did not return phone calls seeking comment on Geron’s planned test.
Dr. Irving Weissman, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine, said he saw no reason the agency should turn down the company or demand that additional non-human tests be done first.
“They better not,” Weissman said, “because then they’re putting themselves right in the way of treating humans for disease.” Weissman is also a board member and co-founder of StemCells, a Palo Alto company that won federal approval in October to transplant adult stem cells into the brains of children to correct a fatal disorder.
If the Geron test gets the OK and proves effective, the company hopes to seek approval eventually for similar tests of human embryonic stem-cell therapies for congestive heart failure, Parkinson’s disease, diabetes and Osteoporosis, among other things.
But other scientists are skittish, including Evan Snyder, director of the stem cell and Regeneration program at the Burnham Institute in La Jolla. He praised Geron for making great progress with its research. Nonetheless, he said the company should do more non-human tests, and make sure their tests precisely mimic the kinds of spinal cord injuries humans get.
“I’m not convinced they have done that yet,” Snyder said.
Cancerous side effects are another worry. Because human embryonic stem cells can become any tissue, Arnold Kriegstein, director of the Institute for Stem Cell and Tissue Biology at UC-San Francisco, fears the injections might trigger tumors. As a result, he said, the FDA and Geron need to be especially cautious.
“The bar would have to be a little higher” for human experiments, Kriegstein said. “There is a great potential for harm.”
Still others are nervous about Geron using a federally approved line of stem cells, many of which have been nourished in so-called feeder layers made from mouse or calf tissue. Studies have found such cells can be contaminated with a molecule that could prompt an immune system attack if injected into humans.
But Geron’s chief executive, Dr. Tom Okarma, said none of those concerns warrant banning human tests.
For one thing, he said, Geron has developed feeder layers that are free of contamination. And to prove it, Geron published data last year that found no Immune Response in mice injected with its human embryonic stem cells.
Okarma said no cancer has turned up in any animals that have received the company’s cells, either.
And although Geron is still compiling data in preparation for filing a formal request to the FDA to do the test, he’s confident from the work already done at UC-Irvine and at his company that the procedure will be safe.
“We’re turning over every stone,” to avoid harming anyone in the experiment, Okarma said. “The last thing in the world a public company wants to do is fall on its nose in its first clinical trial.”
By Steve Johnson
Contact Steve Johnson at (408) 920-5043.