New treatments derived from embryonic stem cells could help paralyzed patients. (Credit: Science Photo Library)
Most of the news headlines on stem cells in recent months have focused on the political maelstrom surrounding morally charged issues.
But, in the labs, scientists are making rapid progress in turning this promising research field into actual medicine. One company, in particular, Menlo Park, CA-based Geron, is taking the lead in developing experimental embryonic stem cell therapies and hopes to begin human trials next year.
Geron’s clinical trial of a therapy to treat spinal cord injuries will likely be the first human test of an embryonic stem cell-based treatment. In preparation for this medical first, the company is trying to figure out how to test a therapy that’s both potentially revolutionary and totally unknown to the doctors who will be carrying out the trials and government officials who will oversee the process.
Geron’s lead therapy has already shown dramatic success in animal models. In 2005, Hans Keirstead, a neuroscientist at the University of California, Irvine, who developed the treatment with funding from Geron, published a paper showing that paralyzed rats injected with the cells were able to walk again.
In Geron’s therapy, embryonic stem cells are the starting ingredient rather than the treatment itself. The embryonic stems cells, which are potentially able to form any human cell type, are transformed into oligodendrocytes — a type of brain cell that wraps itself around neurons, forming a fatty insulation layer that allows electrical messages to be conducted throughout the nervous system. These cells are then injected into the site of the injury, coating neuronal projections that were damaged in the accident and restoring communication to the nervous system.
Because cells are living tissue and their behavior is somewhat unpredictable, trials of cell-based therapies are more complex than trials of conventional drugs. Scientists at Geron have spent years studying their lines of embryonic stem cells, figuring out the precise series of conditions needed to grow giant vats of embryonic stem cells and to transform them into pure populations of oligodendrocytes. The Geron researchers have also developed a way to reliably freeze and thaw the brain cells, so that they can be manufactured in a central location, and then shipped to the hospitals where they will be used. “You can use it off the shelf, just like a pill,” says Thomas Okarma, Geron’s chief executive officer.
Since the successful proof-of-principle experiments were published last year, both Keirstead and scientists at Geron have been running safety tests in animals. “One concern was that potential harm from the transplant was being masked by severity of injury in the animal models,” says Keirstead. So researchers gave the same treatment to animals with mild injuries that usually heal on their own. In a paper published last month, Keirstead showed that the treatment caused no damage and had no negative effect on the normal healing process.
The researchers also want to make sure the transplanted cells don’t develop into teratomas, a type of tumor associated with the injection of embryonic stem cells. Okarma says this is an unlikely side effect, since the Geron treatment is made up of differentiated cells rather than stem cells. Still, the researchers have searched for teratomas under various experimental conditions and seen no signs of the tumors, he says. The company plans to continue safety testing for another year, at the request of the Food and Drug Administration, and will then file for permission to start human tests.
Plans for the trials are already underway, though. According to Okarma, researchers have almost finished the protocol for the experiments and are in discussions with spinal cord injury centers throughout the country that will run the actual tests.
Initial clinical trials will focus on patients with newly acquired, severe spinal cord injuries — those with damage in the thoracic region (between the neck and lower back) who cannot move or feel anything below the site of injury. These patients usually undergo surgery two weeks after the injury to stabilize the spine. For those participating in the trial, surgeons will inject oligodendrocyte cells into the site of the injury. Patients will then be followed for signs of improvement.
The first phase of the human testing will assess mostly safety, which is the conventional procedure in testing new drugs. But rehabilitation therapists will also look for signs of motor improvement, comparing the results with control patients who do not receive the injections. If initial tests are successful, Geron plans to test the therapy in patients with less-severe spinal cord injuries. The company is also developing stem-cell-based treatments for heart disease and diabetes. “We hope to test a new cell type each year,” says Okarma.
Geron’s pilot trial will likely become a test case for future trials of embryonic stem cells treatments. As stem cell research moves from the research lab to human trials, hospitals, doctors, and scientists conducting the tests will face many of the same regulatory and ethical issues faced by scientists using stem cells for research purposes. For example, stem cell research requires complex approval procedures from institutional review boards and an array of ethical oversight boards. “I was shocked to find out many institutions outside California don’t have ESCRO [embryonic stem cell research oversight] committees,” says David Magnus, an bioethicist at Stanford University. “That’s where I think one of the big challenges is going to be.”
Still, scientists are confident they will be able to overcome the obstacles. “Stem cell research is like a plant creeping out of crack in the desert — there’s no way to keep it down,” says Keirstead. “Where it’s allowed to flourish, it blooms.”
By Emily Singer
Copyright Technology Review 2006.