In this phase I clinical trial, doctors affiliated with Oregon Health Sciences University (OHSU) are collaborating with scientists at Stem Cells, Inc., a company based in Palo Alto, Calif. Their immediate goal is limited to healing children afflicted with Batten disease, a rare but fatal neurodegenerative disorder. In the coming decades, however, this work could lead to treatments for neurodegenerative disorders that affect millions, such as Huntington's, Alzheimer's and Parkinson's diseases.
Batten Disease--A Disorder with No Cure
Batten disease is known to experts as neuronal ceroid lipofuscinosis, or NCL. "NCL patients lack an enzyme responsible for breaking down complex fat and protein compounds in the brain," says Robert Steiner, associate professor of pediatrics at the OHSU School of Medicine, and the trial's lead investigator. "These materials accumulate and interfere with normal cell and tissue function and ultimately cause cells to die."
The cellular damage takes an awful toll. "In early infancy or in childhood the children develop seizures. If they ever had the ability to walk or speak, they lose those abilities. It affects the eyes and the vision, so they become blind ... death is inexorable," Steiner says.
Scientists at Stem Cells identified a strain of stem cells that produce the enzyme whose absence causes NCL. In the phase I trial that will take place later this year, Steiner and other surgeons will be injecting six children with these cells, in the hope that they will manufacture the enzyme and halt the disease. For a full year after injection, the researchers will monitor the patients' cognition and vision. They will pay special attention to any possible side effects of the treatment.
"This takes center stage as the first clinical trial that uses stem cells to attempt to possibly treat a disease," says Arnold Kriegstein, director of the Center for Regeneration Medicine at the University of California, San Francisco. If successful, the study could pave the way for stem cell therapies to be used on conditions such as Alzheimer's, Parkinson's and stroke. But, he cautions, "the first criterion is to see whether these stem cells will be safe."
The Dangers of Stem Cell Therapy
In some cases, uncontrolled growth of neural stem cells has been linked to malignant brain tumors. The researchers chose fetal neural stem cells--obtained from a company that procures tissue from aborted fetuses with the consent of the mothers--because such cells are unlikely to develop into anything other than cell varieties already found in the brain. If embryonic stem cells were used, they might grow into bone, hair or eye tissue, to disastrous effect.
Cancer is not the only kind of trouble that could occur. "The hope is that these cells will do nothing more than diffuse or distribute themselves and pump out this enzyme," Kriegstein says. "There may be some problems if they start turning into cell types that cause mischief, [such as] nerve cells that might start forming circuits and shifting activity."
As therapeutic agents in the brain, stem cells have several advantages over traditional therapies. The blood-brain barrier blocks many drugs on which doctors might otherwise rely. Stem cells injected past this barrier can migrate to regions where they are needed and develop into new brain cells. Because they can survive indefinitely, there should be no need for repeated surgery. Researchers must, however, tailor therapy to the challenges of each disease.
In the Batten trial, the stem cells are being used for their ability to produce and deliver enzymes, rather than their potential to develop into new neurons. Experts believe that several brain disorders, including Huntington's and Alzheimer's, would benefit from a similar approach in which stem cells would secrete hormones to protect existing neurons from further damage.
The Future of Neural Stem Cell Therapy
In the early 1990s, as part of therapy designed to restore neural function in patients with Parkinson's, Curt Freed, a neurosurgeon at the University of Colorado, performed transplantations of cells derived from fetuses. Now, however, "we're moving into an era in which we'll create cells in the laboratory," Freed says. "I see the cell therapy area as becoming very sophisticated during this century. Two hundred years ago, drugs were not pure products but were ground-up leaves." Today, chemists can refine drugs to nearly 100 percent purity. "I think exactly [the same thing] is going to happen with cell therapy," he predicts.
That is the business model of Stem Cells Inc., which purifies fetal cells, multiplies them a thousandfold, and freezes them in "cell banks" for individual patient use. A cell population grown by this technique is much more uniform than the original sample, which should keep results consistent from patient to patient. "Because we can bank and store them," explains Rodney Young, CFO of Stem Cells, the company expects eventually to profit as the pharmaceutical industry does, by selling a product--"stem cells in a bottle."
Even though the primary goal of the initial Batten trial is to discover whether or not the treatment is safe, the OHSU/Stem Cells researchers expect that the doses of stem cells used in this trial could have therapeutic effect in the children. "We certainly will publish the results & whether they are positive, negative or neutral," Steiner says. In the meantime, "we don't think it's helpful to have a lot of hype about this study. We just want to do our work and take care of the children as best we can."
Twenty-eight days after the surgery, the parents of the first patient in the Batten trial held a press conference to thank the doctors involved. "There were doctors and nurses and so many specialists & it was a symphony of love for our son," says Marcus Koerner, the father. "The first news we got was that the first injection of neural stem cell--transplant cells--had gone in & everyone was so elated."
The boy emerged from surgery with a shaved head and incision scars. Steiner and the other surgeons warned the parents of possible side effects but all has gone smoothly so far. The child, who had seizures before the surgery, has had none since and has even spoken words the parents have not heard in a long time. With Batten disease, language ability can fluctuate and this improvement may have been caused by the support the child experienced in the hospital. "We are way too early in the uncharted territory [to be certain the surgery has had a beneficial effect] & but as parents," Koerner says, "we are overjoyed."