DISEASE REPLICATED, CONTRIBUTING CELL FOUND IN 2 STUDIES
By Jamie Talan
NEWSDAY
Scientists at Columbia University Medical Center have identified a new player in the motor neuron disease that claimed the life of baseball legend Lou Gehrig, and their scientific collaborators at Harvard Medical School have used stem-cell technology to re-create the disease process in a lab dish.
These developments, reported this week in two papers in the journal Nature Neuroscience, could help unravel the causes of the fatal disease and allow scientists to test the effects of drugs against damaged motor neurons grown from stem cells in the lab.
There are 30,000 Americans with ALS (amyotrophic lateral sclerosis), and it is always fatal. The average survival after diagnosis is five years, and there are no treatments that halt or prevent motor neurons in the brain from dying. Paralysis results because the brain no longer can talk to these neurons that control muscles.
Until recently, ALS researchers have focused on the motor neurons themselves.
But Columbia scientist Serge Przedborski, co-director of the Center for Motor Neuron Biology and Disease, and his colleagues showed that non-neuronal support cells called astrocytes that carry the mutant form of the ALS gene can on their own cause normal motor neurons to get sick and die. That means, said Przedborski, that astrocytes are intimately involved in the disease process. If so, this discovery could provide a new route to developing treatments to prevent or slow the disease.
The team identified a toxic molecule in the astrocytes that seems to trigger damage to motor neurons, and scientists are now working to name the rogue molecule. The Columbia researchers are collaborating with Harvard scientists to unravel the puzzle of ALS.
In the Harvard study, Kevin Eggan and Tom Maniatis used embryonic stem cells to make a population of diseased motor neurons grow.
"We thought that embryonic stem cells could provide a system in which to study ALS," said Eggan, of Harvard's Stem Cell Institute. Indeed, the stem cells were coaxed into making motor neurons from the mutant form of the SOD1 gene, the most common familial ALS gene.
The pathology in the Petri dish was similar to that seen in a mouse with the disease. These specialized stem cells can make billions of motor neurons that will succumb to the damage caused by the mutated gene, the scientists said. Motor neurons are labeled with a green fluorescent protein, which makes them easy to identify.
"This is a viable approach," said Eggan, referring to the use of the green protein. "It's difficult to pick out damaged motor neurons from animal models. We will be able to use this system to do drug screening."
Much of the excitement over stem cells has surrounded their role in possible therapies. This study shows that stem cells also can be used to understand diseases, the researchers said. Eggan likens the study of disease to the way investigators used to figure out why a plane crashed.
Engineers would rush to the crash scene and study the broken pieces. Often, there was so much damage that it was impossible to figure out the events that led to the crash. Today, black boxes on planes collect those missing early events and have helped enormously in putting the pieces together.
The embryonic stem cells that carry disease genes, Eggan said, are the equivalent of the plane's black box. "These cells allow us to replay the early events of the disease process."
