August 5, 2003
Hilary Waldman, The Hartford Courant
The Record, Bergen County, NJ
Scientists at Yale think cells from bone marrow might hold promise for repairing nerve cells damaged by spinal-cord injuries and diseases such as multiple sclerosis.
Although the research is in its infancy and the technique faces huge biological and practical obstacles, the first safety testing in humans could begin within a year.
"The beauty of the potential use of bone marrow is you don't have to go into the brain to remove nerve [stem] cells," said Dr. Jeffery Kocsis, associate director of the Neuroscience and Regeneration Research Center of Yale University.
Kocsis and his colleagues, whose labs are on the grounds of the Veterans Administration Medical Center in West Haven, Conn., have already transplanted specialized stem cells from adult bone marrow into rats and produced substantial regrowth of important nerve cells.
The idea is especially tantalizing for the treatment of MS, a disease in which the body's immune system attacks and destroys a substance called myelin, the fatty coating that insulates nerve cells in the brain and enables impulse conduction.
Without myelin, nerves cannot effectively send messages to distant parts of the body. The destruction can cripple MS victims, causing problems with vision, balance, movement, and cognitive function.
Finding ways to restore the myelin coating has become one of the hottest areas of MS research in the last two or three years, as the promise of using immature cells, known as stem cells, to repair many broken body parts has progressed.
But restoration of the central nervous system holds particular challenges, said Stephen Reingold, vice president for research at the National Multiple Sclerosis Society.
Scientists have long believed that nerve cells do not repair themselves like other parts of the body but have found some cells with stem cell-like qualities in the nose and frontal lobe of the brain. Removed from the body and isolated in a dish, these cells can divide and produce large numbers of stem cells. When the cells are re-implanted in a rat's brain, they seem to create new brain cells.
To harvest these cells, however, doctors must remove a sample of brain tissue, possibly causing damage. Tissue removed during brain surgery on others also could be used, but that raises the specter that the borrowed cells will be rejected.
Using a patient's own bone-marrow cells could prevent both of those problems.
Dr. Timothy Vollmer, chairman of neurology at the Barrows Neurological Institute in Phoenix, Ariz., and one of the nation's leading MS researchers, called bone-marrow stem-cell transplantation among the most "attractive" approaches to repairing damaged nerve linings.
Vollmer has experimented with transplanting myelin-forming cells from the ankle into the brains of a few MS patients to find out if the cells from outside the central nervous system can stimulate repair in the brain. The results have not been published.
He said the potential in bone marrow may cut 10 years off the time it may take to develop a safe, practical, and effective way to restore function in people disabled by MS.
Meanwhile, more intense physical therapy and recently discovered nerve-cell growth factors may offer the most immediate hope for restoring function in MS patients.
Though it has long been known that nerve cells naturally find new routes around damaged pathways, restoring function, Vollmer said, he believes that more intensive physical rehabilitation combined with the growth factors will make the recovery more efficient.
Those approaches will be important while researchers work around the ever-unfolding complexities of nerve regeneration.
As scientists gain a greater understanding of how MS does its damage, they have discovered that myelin is "more complicated than rubber insulation around an electrical wire," Reingold said.
In healthy people, there seems to be some kind of understanding between the myelin coating and the nerve cells that too much myelin is not a good thing. Another group of Yale scientists has identified a protein that seems to signal myelin to stop growing when the correct amount has formed around the nerve.
The protein, however, does not seem to recognize when old myelin has been destroyed and needs repair. The protein blocks the growth of new myelin even in patients who need new insulation.
"Before you can grow myelin, you have to turn off the immune response and turn off the myelin inhibitory process," Reingold said.
Nonetheless, Reingold said, while Kocsis and his colleagues are probably standing at the base of a mountain with a daunting climb ahead, their research offers huge potential for the treatment of people with spinal-cord injuries, Parkinson's disease, and other damage to the central nervous system, including MS.
Kocsis acknowledges that the use of bone-marrow stem cells to repair nerve cells is preliminary, but he said he would consider testing a transplant on a human subject soon to find out if these cells cause any damage or injury to the patient. Testing the safety of a technique is the first step toward finding out whether it actually works.
"There's so much exciting work that happens in a controlled environment,"
Kocsis said. "The problem is to bring it to humans."
Copyright © 2003, The Record, Bergen County, NJ