Copyright 2004 The Baltimore Sun Company
All Rights Reserved  
The Baltimore Sun
October 25, 2004 Monday FINAL Edition
SECTION: TELEGRAPH, Pg. 1A
LENGTH: 1098 words
HEADLINE: Stem cell findings stir science forum;
Advances: Repair of paralyzed rats' spinal cords holds promise.
BYLINE: David Kohn
SOURCE: SUN STAFF
DATELINE: SAN DIEGO

SAN DIEGO -- Scientists here said yesterday that they had used human stem cells to repair the damaged spinal cords of paralyzed rats and enable them to walk, an important advance that could result in human trials by 2006.

This was the first time stem cells have been successfully used to treat such spinal cord injuries.

The research findings were announced at the annual conference of the Society for Neuroscience. Researchers here also disclosed several other new stem cell discoveries relating to a range of neurological disorders, including brain cancer and Parkinson's disease.

"This is incredibly promising. It shows how quickly the field is moving," said Evan Snyder, director of stem cell research at the Burnham Institute in San Diego. Snyder presented his own work yesterday, showing that stem cells have potential to deliver a lethal blow to a currently untreatable type of brain cancer.

In a similar vein, University of Wisconsin researcher Clive Svendsen said he had successfully used stem cells as a delivery mechanism, in this case for a powerful protective protein that significantly slowed the progression of Parkinson's disease.

But it was the spinal cord work that generated the most excitement and seemed most likely to be tried in humans first. "The degree of recovery we see in these animals is tremendous," said University of California, Irvine neuroscientist Hans Keirstead, who led the research. "This is a very big deal."

Keirstead succeeded in transforming human embryonic stem cells into a cell called an oligodendrocyte. These cells form the fatty substance myelin, which forms a sheath of insulation around nerve cells. Without this insulation, the nerve cells can't transmit messages. After injury, nerves in the spinal cord are often unable to regrow myelin. Even if the nerve cell regenerates, it is useless without myelin.

Keirstead transplanted the human oligodendrocytes into the spinal cords of injured rats. After nine weeks, the animals regained the ability to walk. "It's not perfect -- they're not playing soccer," Keirstead said of the rats. "But they're doing extremely well."

The treatment only worked when the stem cells were implanted soon after the spinal cord injury. In rats injured ten weeks prior to the treatment, the stem cells had no effect. Keirstead suspects that scarring around the nerve cells may block the new myelin from forming properly.

Some researchers were more cautious about Keirstead's results, noting that spinal cord research is littered with examples of seeming breakthroughs that ultimately proved unsuccessful. "The Keirstead study looks encouraging. But animal models don't always translate to humans," said Dennis A. Steindler, a neuroscience professor at the University of Florida.

Stems cells are specialized cells which can be transformed into a wide range of other cells. Some researchers think stem cells can eventually treat or cure a wide range of diseases, supporting or even replacing damaged tissue anywhere in the body.

But because some of the cells are taken from embryos, which must be destroyed during the process, the field has become controversial.

Some critics say that harvesting stem cells from embryos is immoral. In August, 2001, President Bush tried to address these concerns by limiting federal funding of embryonic stem cell research. Only work using stem cells collected before his order is eligible for federal funds. Researchers are not prohibited from using other embryonic stem cell "lines," as they are called, but they cannot use government money in this work.

Many stem cell researchers have decried this limitation, saying it has hampered their work. Stem cells have become a major issue in the presidential race, with Democrat John Kerry promising to lift the restrictions if he is elected. The Bush campaign has countered in part by saying that it's not clear that stem cell research can lead to useful medical treatments.

"We don't even know that stem cell research will provide cures for anything," first lady Laura Bush said in a speech in Pennsylvania this month.

Snyder sharply criticized this stance. "It's a totally misinformed, uneducated opinion," he said. "They don't know what's happening. They're not reading the literature."

Over the past few months, Snyder has been heavily involved in promoting Proposition 71, a California ballot initiative that would set aside more than $3 billion over the next ten years for stem cell science. The California plan is the largest of several being crafted by states and large private institutions to create non-federal sources of funding for the research.

Not all the research involved embryonic stem cells. Snyder's research used human neural stem cells, which are taken from fetal tissue. While still malleable, these cells can only be transformed into neuronal tissue. Snyder and his colleagues took advantage of the cells' well-known but as-yet-unexplained propensity to home in on tumor cells. The scientists used genetic engineering to arm the cells with a powerful tumor-killing substance and transplanted the cells into the brains of mice with a particularly lethal brain cancer called intracranial glioblastoma.

The stem cells traveled throughout the brain, attacking tumors and sharply reducing their size. "It worked in a big way," said Snyder, who thinks the therapy is ready for human trials, in part because the cancer is incurable. "If ever there was a low-risk, high-yield approach to dealing with a bad disease, this is it," he said.

Svendsen, the University of Wisconsin scientist, also used fetal tissue to derive neural stem cells. He genetically modified these cells so they produced a protein called glial-derived neurotrophic factor (GDNF), which can protect and nurture neurons.

He then transplanted the engineered stem cells into the brains of rats that had a Parkinson's-like condition. In humans, the disease destroys neurons in a key part of the brain, causing patients to lose control of their movements. The stem cells delivered the GDNF, which increased the health of the vulnerable neurons. Svendsen is now studying the treatment in monkeys.

Svendsen suspects that the therapy might have even wider application. GDNF is a powerful guardian and might be able to ward off all kinds of neurodegenerative diseases. "If we can do it for Parkinson's," he said, "we can do it for other diseases."