Researchers have for the first time been able to generate a pluripotent stem cell line from the cells of a patient with a genetic disease, according to a study appearing tomorrow (August 1) in Science. The scientists successfully reprogrammed skin cells from an 82-year-old patient with Amyotrophic Lateral Sclerosis (ALS) into healthy motor neurons.

"It's a stunning accomplishment," Neil Cashman, professor of neurology at the University of British Columbia who was not involved in the study, told The Scientist. "That they take somebody at the end of their life with a chronic disease and can still reprogram the cells -- it's a slam dunk."

The researchers, led by Kevin Eggan at Harvard University, infected the diseased cells with genetically modified viruses coding for the four transgenes Klf4, OCT4, SOX2, and c-Myc, the same cocktail of genes used by one of two groups last November in the first reprogramming studies. The cells containing the mutation SOD-1, which is responsible for the familial form of ALS, were successfully reprogrammed (into iPS cells) and differentiated into motor neurons.

There are a couple of caveats to the findings, however. Firstly, the team did not show that the motor neurons developed the pathology of the disease. "The next major question is whether the ALS motor neurons are in any way different to those from non affected patients," Clive Svendsen, neurologist at University of Wisconsin, Madison, who was not involved in the study, wrote in an Email to The Scientist. The researchers are confident that in time the cells would show the marked deterioration associated with ALS, Eggan told reporters during a teleconference. In addition, the team found that some of the tumorigenic genes required for reprogramming were downregulated when they differentiated the cells into neurons, but some continued to be expressed. "This is worrisome," said Cashman. Using genetically altered cells that express tumorigenic genes is still too dangerous for patient application, said Eggan.

Perhaps the most important caveat to the study, however, was that it did not demonstrate the ability of the motor neurons to establish connections in vivo with muscle fibers and integrate into the nervous system. For now, the reprogrammed cells will be a boon to laboratory research, said Eggan. "Because those stem cells harbor the genes which ultimately led to the disease in the patient, if we could produce cell types that become sick, we can use them in the laboratory to understand aspects of disease -- we take the study of disease out of patients and put it in the Petri dish."

The cells may give researchers the opportunity to study the mechanisms that lead to the disease in the first place. "The mechanism is the key in our attempt to find a cure," Christopher Henderson, from Columbia University and coauthor on the study, said on the teleconference. "Using these degenerative iPS cells we can develop compounds that prevent that degeneration."

And, even though SOD-1 is responsible for less than 5% of all ALS cases, Henderson added, "Our real hope is that similar events are occurring in sporadic cases [of the disease] in which the trigger is different." Since the phenotypes of the genetic and the sporadic disease are so similar, he added, they believe there may be a similar mechanism at work.



Correction: The original version of this story incorrectly spelled the disease. A correction has been made, The Scientist regrets the error.