Stem Cells An Unlikely Therapy for Alzheimer's
Reagan-Inspired Zeal For Study Continues
By Rick Weiss
Washington Post Staff Writer
Thursday, June 10, 2004; Page A03
Ronald Reagan's death from Alzheimer's disease Saturday has triggered an outpouring of support for human embryonic stem cell research. Building on comments made by Nancy Reagan last month, scores of senators on Monday called upon President Bush to loosen his restrictions on the controversial research, which requires the destruction of human embryos. Patient groups have also chimed in, and Senate Majority Leader Bill Frist (R-Tenn.) on Tuesday added his support for a policy review.
It is the kind of advocacy that researchers have craved for years, and none wants to slow its momentum.
But the infrequently voiced reality, stem cell experts confess, is that, of all the diseases that may someday be cured by embryonic stem cell treatments, Alzheimer's is among the least likely to benefit.
"I think the chance of doing repairs to Alzheimer's brains by putting in stem cells is small," said stem cell researcher Michael Shelanski, co-director of the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at the Columbia University Medical Center in New York, echoing many other experts. "I personally think we're going to get other therapies for Alzheimer's a lot sooner."
Stem cell transplants show great potential for other diseases such as Parkinson's and diabetes, scientists said. Someday, embryo cell studies may lead to insights into Alzheimer's. If nothing else, some said, stem cells bearing the genetic hallmarks of Alzheimer's may help scientists assess the potential usefulness of new drugs.
But given the lack of any serious suggestion that stem cells themselves have practical potential to treat Alzheimer's, the Reagan-inspired tidal wave of enthusiasm stands as an example of how easily a modest line of scientific inquiry can grow in the public mind to mythological proportions.
It is a distortion that some admit is not being aggressively corrected by scientists.
"To start with, people need a fairy tale," said Ronald D.G. McKay, a stem cell researcher at the National Institute of Neurological Disorders and Stroke. "Maybe that's unfair, but they need a story line that's relatively simple to understand."
Human embryonic stem cells have the capacity to morph into virtually any kind of tissue, leading many scientists to believe they could serve as a "universal patch" for injured organs. Some studies have suggested, for example, that stem cells injected into an injured heart can spur the development of healthy new heart muscle.
Among the more promising targets of such "cellular therapies" are: Parkinson's disease, which affects a small and specialized population of brain cells; type-1 diabetes, caused by the loss of discrete insulin-producing cells in the pancreas; and spinal cord injuries in which a few crucial nerve cells die, such as the injury that paralyzed actor Christopher Reeve.
In part as a result of her friendship with Hollywood personalities Doug Wick, Lucy Fisher, and Jerry and Janet Zucker -- all of whom have become stem cell activists because they have children with diabetes -- Nancy Reagan became interested in stem cells and their oft-cited, if largely theoretical, potential for treating Alzheimer's. Over the years, she has become more vocal on the issue.
On May 8, with her husband's brain ravaged by Alzheimer's disease, Nancy Reagan addressed a biomedical research fundraiser in Los Angeles and spoke out forcefully.
"I just don't see how we can turn our backs on this," she said, in an oblique cut at Bush, who placed tight limits on the field in August 2001 to protect, he said, the earliest stages of life.
Since Reagan's death, many others have joined the call to enlist embryonic stem cells in the war on Alzheimer's, including some new converts. Among the 58 senators who signed the letter to Bush were 14 Republicans and several abortion opponents -- evidence that the Reagan connection is providing "political cover," said Sean Tipton of the Coalition for the Advancement of Medical Research, a stem cell advocacy group.
But in contrast to Parkinson's, diabetes and spinal injuries, Alzheimer's disease involves the loss of huge numbers and varieties of the brain's 100 billion nerve cells -- and countless connections, or synapses, among them.
"The complex architecture of the brain, the fact that it's a diffuse disease with neuronal loss in numerous places and with synaptic loss, all this is a problem" for any strategy involving cell replacement, said Huntington Potter, a brain researcher at the University of South Florida in Tampa and chief executive of the Johnnie B. Byrd Institute for Alzheimer's Research.
"We don't even know what are the best cells to replace initially," added Lawrence S.B. Goldstein, who studies stem cells and Alzheimer's disease at the University of California at San Diego. "It's complicated."
Goldstein and others emphasized that future Alzheimer's patients could benefit if stem cell research is allowed to blossom.
Scientists suspect, for example, that stem cell studies could help identify the molecular errors that underlie Alzheimer's, which in turn would help chemists design drugs to slow or even reverse the disease.
But that line of work could face formidable political hurdles. That is because the most frequently cited approach would require not just stem cells from spare embryos donated by fertility clinics -- a currently untapped source of cells that many want Bush to make available to federally funded researchers. It would also require the creation of cloned human embryos made from cells taken from Alzheimer's patients.
From such embryos, stem cells bearing the still-unidentified defects underlying Alzheimer's could be removed and coaxed to grow into brain cells in lab dishes, and their development could be compared to the development of normal brain cells.
While that experiment could shed important light on the earliest -- and perhaps most treatable -- stages of Alzheimer's, a majority in Congress have said that the creation of cloned human embryos is an ethical line they are unwilling to cross.
Less controversial uses of stem cells may also lead to insights, Goldstein and others said. The key, said Harvard stem cell researcher George Daley, is not to get "preoccupied with stem cells as cellular therapies." Their real value for Alzheimer's will be as laboratory tools to explore basic questions of biology, Daley said.
Unfortunately, said James Battey, who directs stem cell research for the National Institutes of Health, "that is not necessarily the way I hear the disease community talking. They tend to focus on the immediate use of stem cells for their disease or disorder."
It is not clear whether the recent wave of stem cell support will persist as it becomes clearer that cures remain far off -- and, in the case of Alzheimer's, unlikely. Basic research with stem cells is just as deserving of support as therapeutic trials, Battey said, "but it's a much harder sell."
"The public should understand that science is not like making widgets," he said. "We're exploring the unknown, and by definition we don't know where it's going to take us."
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