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A Step Closer To Understanding Scientists hope success in mice study can be used as a model of cells' potential in fighting brain diseases BY JAMIE TALAN - STAFF WRITER November 15, 2004 Recently, Harvard scientists discovered that, at least in mice, the brain can rally against an all-out attack on brain cells by summoning stem cells to help repopulate the hard-hit region. Now the researchers want to determine whether similar stem cell activity can be orchestrated in diseases like ALS or Parkinson's, in which a specific group of brain cells dies off. Such a finding would lead toward an understanding of how to achieve similar results in the human brain, said Jeffrey Macklis, director of the Massachusetts General Hospital-Harvard Medical School Center for Nervous System Repair. "The goal is to investigate whether this once science-fiction idea of activating the birth of new neurons within the brain can be achieved," Macklis said. "We are not there yet, but it is the long- term goal." The promise of stem cells - immature cells that can take orders to become virtually any cell in the body - offers hope for a variety of diseases. The finding is one of several recent discoveries in which science is widening its understanding, as researchers aim to coax stem cells into taking on specific jobs. The field is still in its infancy, and studies are conducted on small critters engineered to have the equivalent of human diseases. The Harvard research, reported in the Proceedings of the National Academy of Sciences earlier this month, relied on mice. Researchers destroyed a population of neurons that die in amyotrophic lateral sclerosis, commonly known as ALS or Lou Gehrig's disease, and spinal cord injury. They then tagged stem cells that moved to areas in the brain involved in motor control, and found that the stem cells behaved just as mature motor neurons do: They migrated from the brain into the spine. The hope is that these neurons, and the new connections that they make in the spine, will repair the communication between nerve cells and aid in restoring movement. "Rebuilding this circuitry could be used to regain motor function," Macklis said. But it's a field mired in controversy because the easiest way to cull stem cells is from embryos, and the only source is discarded embryos frozen in in vitro fertilization clinics or from abortions. A directive issued by President George W. Bush in 2001 prohibits use of federal funds to develop new lines of stem cells. Attempts to isolate and develop sources that are not embryonic are under way, and recent discoveries have found that stem cells found in bone marrow can be turned into neurons and supporting brain cells. Such a finding has led to speculation that a person's own bone marrow could be used to make cells for treatments of specific diseases. Macklis and his colleagues are working to understand the molecular orders the cells they identified need to respond to the damaged brain. Their work started with the depletion of tens of thousands of neurons at once. In the immediate aftermath, they found 30 to 50 new neurons per cubic millimeter. After two months, only 10 percent of the neurons survived - but a year later, they were still present. The study is continuing in an effort to determine whether the cells, which eventually sent connections down to the spine, were functioning. In other recent work, scientists at Johns Hopkins Medical Institutes reported last month that they isolated heart stem cells from adult humans and other animals and were able to grow them in batches in a lab dish. The goal is to use them to replenish the damaged heart. And Dr. Steven Goldman and his colleagues at University of Rochester Medical Center have made a discovery that he said could lead to a clinical trial in Huntington's patients within two years. There are no available treatments. Like all stem cell scientists looking to treat brain disease, Goldman has aimed at reshaping the adult brain's store of stem cells. Less than a decade ago, scientists discovered that the adult brain has immature stem cells in two areas - the ventricular zone and the olfactory system. Goldman says these stem cells normally become support cells, or glia, that help neurons carry out their job. Scientists have characterized glia as the workhorses of the brain, and neurons as the generals. But his lab is taking the glia cells from the olfactory bulb of mice and turning them into neurons capable of restoring the damaged brain. Researchers used a gene to pump brain-derived growth hormone - considered important for stem cell growth - into one of the stem cell zones. They found that when the stem cells of this region were bathed in a growth hormone called brain-derived neurotrophic factor, some of the glial cells developed into the kind of neurons that are lost in Parkinson's and Huntington's. They then used another gene to block a protein that tells stem cells to mature into glia, and showed they could shut down production of glial cells and ramp up production of neurons in numbers that Goldman said could have clinical impact. The findings were presented last month at the Society for Neuroscience meeting in San Diego. Mice in the experiment had a genetic mutation that causes Huntington's disease. Normally they would become very sick at 10 weeks, and those in the lab didn't get sick until they were 4 months old and lived almost twice as long as expected. "The haze is really coming off the field," Goldman said. "We are beginning to understand where stem cells would work, and what the clinical opportunities will be." SOURCE: New York Newsday, NY http://tinyurl.com/6dcbs * * * Murray Charters <[log in to unmask]> Please place this address in your address book Please purge all others Web site: Parkinsons Resources on the WWWeb http://www.geocities.com/murraycharters ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn