In amyotrophic lateral sclerosis (ALS), the degeneration and subsequent loss of motor neurons leads to progressive, and eventually fatal, paralysis. Efforts to determine the mechanisms that underlie this degeneration have thus far been hampered by the impracticable need to remove samples of affected spinal cord from living patients. However, a study recently published in Science showed that it is now possible to circumvent this obstacle.
The researchers used viral gene delivery to transform skin cells from two elderly sufferers of a genetically inherited form of ALS into induced pluripotent stem (iPS) cells, the first time that this has been achieved with mutant cells. Next they made these iPS cells differentiate into motor neurons, and thereby obtained a plentiful supply of genetically mutant neuronal tissue for investigation.
“No one has ever managed to isolate these neurons from a patient and grow them in a dish,” said lead author Kevin Eggan, of Harvard University. “Now we can make limitless supplies of the cells that die in this awful disease [...] study these neurons in a lab dish and figure out what's happening.” ( Independent , 1 August 2008.)
“This is a seminal discovery,” commented Valerie Estess, of non-profit organization Project ALS. “For the first time, researchers will be able to look at ALS cells under a microscope and see why they die.” ( Telegraph , 1 August 2008.)
A lot of work remains to be done, and the first step will be to see if these neurons degenerate like those of patients with ALS. However, according to Kathrin Plath, a stem cell researcher at UCLA who was not involved in the study, these results represent “...an important step that should allow the development of experimental and therapeutic interventions for this disease.” ( LA Times , 1 August 2008.)
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Nicholson, C. Motor neurons galore. Nat Rev Neurosci 9, 659 (2008). https://doi.org/10.1038/nrn2487