A team of researchers from the Harvard Stem Cell Institute (HSCI) and Columbia
University, in a collaboration catalyzed by the Project A.L.S./Jenifer Estess
Laboratory for Stem Cell Research, has demonstrated that pluripotent stem cells
generated from a patient with ALS (amyotrophic lateral sclerosis) can be
directed to differentiate into motor neurons - the very brain cells destroyed by
ALS. The results of the team's study appear in the online issue of
. This is the first published report to show that disease-specific
stem cells may be derived from an individual patient.
In the study, led
by Kevin Eggan, of the Harvard Stem Cell Institute, skin cells taken from a
patient with a familial form of ALS were induced to become pluripotent stem
cells. Scientists then differentiated the pluripotent cells into motor neurons
and glia (support cells in the brain) that featured an ALS genotype.
"This is a seminal discovery," said Valerie Estess, director of research
for Project A.L.S. "The ability to derive ALS motor neurons through a simple
skin biopsy opens the doors to improved drug discovery. For the first time,
researchers will be able to look at ALS cells under a microscope and see why
they die. If we can figure out how a person's motor neurons die, we will figure
out how to save motor neurons."
Starting in 1999, Project A.L.S.
recruited leading scientists and clinicians to define the potential role of stem
cells in understanding and treating ALS, the fatal neurodegenerative disease,
also known as Lou Gehrig's disease. Project A.L.S.-funded scientists began by
transplanting stem cells directly into mice with ALS, with limited success. More
recent experiments have shown that stem cells may be more valuable as tools to
understand the disease process and create mini-representations of disease - or
assays - for the purpose of drug screening.
"For the first time, we have
the opportunity to examine cellular and molecular defects in motor neurons and
glial cells derived from patients with ALS. And we can now begin drug screens on
disease-specific classes of human motor neurons," said Thomas Jessell, a Howard
Hughes Investigator at Columbia University, and Project A.L.S. advisor. "Through
the work of the Jenifer Estess Laboratory for Stem Cell Research we now can
glimpse the new age of ALS research, an age of progress and promise."
Co-author on the paper, Christopher Henderson, who is co-director of the
Columbia University Center for Motor Neuron Biology and Disease, and senior
scientific advisor to the Project A.L.S. Laboratory, said: "It has been a
privilege to collaborate with Kevin Eggan and his team and to contribute to this
critical step forward. We will continue to work hand-in-hand with Harvard
researchers and Project A.L.S. to exploit the potential of these cells for drug
Three years ago, Project A.L.S. asked Dr. Eggan, a stem cell
expert, and Chris Henderson, Hynek Wichterle, as authorities on motor neuron
biology and drug screening at Columbia University, to work together to
understand ALS, one of our most complicated and devastating neurological
disorders. This publication marks the first major breakthrough of this