Boosts for ALS research
A $15-million grant to Columbia and a new private lab are both aimed at roots of the degenerative disease
Source: Newsday.comBY JAMIE TALAN
Newsday Staff Writer
May 30, 2006
On a recent spring day, Leonard Tow orchestrated his own private classical concert for his wife of 54 years. Claire Tow, 76, can no longer speak, the motor neurons in her vocal cords damaged by amyotrophic lateral sclerosis, commonly known as Lou Gehrig's disease or ALS. But the disease has not stopped the Connecticut wife, mother and grandmother from celebrating life, including reveling in the private concert her husband arranged at their home.
Now the Tows are conducting a grand symphony of another sort. They recently donated a $15-million matching grant to Columbia University Medical School to study motor neurons - and to try to crack the puzzle of ALS. The motor neuron center is already up and running with participation from at least 40 different laboratories at Columbia, all with the goal of unraveling the biology of the vulnerable motor neurons and figuring out treatments.
And down the street from Columbia's Motor Neuron Center, a separate laboratory opened May 15, also focusing on motor neurons but from a different angle: to develop the first human embryonic stem cell lines for the neurons. The lab is funded by Project ALS, a Manhattan-based organization started by the three Estess sisters, one of whom had ALS. Columbia's facility will collaborate with the private lab, but the two are funded separately to comply with federal rules on stem cells.
Jenifer Estess' first signs of motor neuron disease appeared in 1997. She died in 2003, only months before her book, "Tales From the Bed," was published.
Now, her sisters, Valerie and Meredith, have raised money to study human embryonic stem cells in New York. Federal funding of human embryonic stem cell research is prohibited, and financial support must come from private donations. The work must be done in separate facilities to ensure that the university doesn't lose its federal funding for other research.
"Project ALS had the idea to start a freestanding lab at Columbia," said Valerie Estess, who directs Project ALS. Columbia scientists discovered in 2002 that they could direct embryonic stem cells into becoming functional motor neurons in a mouse. Now, the hope is to do the same thing with human embryonic stem cells, Estess said.
"We hope we can get human stem cells that represent the sporadic form of ALS," said Christopher Henderson, a professor of pathology and neurology at Columbia and co-director of the Motor Neuron Center.
In the United States, between 25,000 and 30,000 people are living with ALS, and 8,000 new cases are diagnosed every year. The disease destroys the motor neurons, which make muscle movements possible. The life span from diagnosis to death ranges from two to five years. So far, there are no clues to treatments that could protect or reverse motor neuron death.
At the helm of Columbia's elaborate scientific research into ALS is Thomas Jessell, a Howard Hughes Medical Institute investigator and professor in the department of biochemistry and molecular biophysics at Columbia. "It is an opportunity to take advantage of the wealth of knowledge in neuroscience," Jessell said. "This wonderful philanthropy has really mobilized us."
The Columbia team will collaborate with Harvard scientists working at perfecting human nuclear transfer, the same breakthrough technology that recently unraveled in the hands of South Korean scientists. The idea is to take fibroblasts, or skin cells, from ALS patients at Columbia and send them to Harvard, where Douglas Melton and his colleagues will attempt to fuse the genetic material into a human egg cell with its own nucleus removed. The hope is to create human embryonic stem cells that express motor neurons.
Henderson, Jessell and Hynek Wichterle, also of Columbia, are trying to understand the developmental processes that lead to the generation of motor neurons. With this knowledge in hand, they hope to generate high numbers of motor neurons to study the disease process and begin to identify treatments that could stall or reverse the death of these motor neurons.
Wichterle figured out how to get mouse embryonic stem cells to make motor neurons. They've created a mouse that generates motor neurons that light up fluorescent green.
"It would be great to have embryonic stem cells that replicate the motor neuron disease process in humans," Wichterle said.
Big questions remain: Why are motor neurons so susceptible to damage? Could there be a way to replace dying motor neurons or stimulate new populations of them? Can scientists identify ways to treat this disease?
Right now, Claire Tow and others with ALS are living under a death sentence. Tow has tried an experimental drug called minocycline, the anti-inflammatory Celebrex and the nutritional supplement co-enzyme Q10.
"She's tried every flavor of the day," her husband said. "We don't know whether anything helped."
The Columbia scientists also are setting up laboratories to test experimental compounds.
"This is a complicated disease," Jessell said. "The best contribution is to provide the best rational science."
Copyright 2006 Newsday Inc.