Induced Pluripotent Stem Cells Generated from Patients with ALS Can Be Differentiated into Motor Neurons.

ALS Breakthrough!
Scientists in the US have converted skin cells from an 82-year-old woman with amyotrophic lateral sclerosis (ALS) into stem cells that formed motor neurons with the same genetic make up as the patient. The breakthrough opens the possibility of modelling a patient's specific disease outside of the patient, to improve investigation and drug screening, and perhaps even to develop new neurons to replace the damaged ones in the patient.

The breakthrough is written up as a study in the 31st July online issue of Science, and was the work of Dr Kevin Eggan, a biologist at the Harvard Stem Cell Institute, and other colleagues from Harvard University in Cambridge, Massachusetts, and Columbia University, New York.

ALS, also known as Lou Gehrig's disease, is a progressive degenerative disease that attacks the motor neurons in the spinal cord, leading to paralysis of limbs and respiration.

Eggan told a press conference that by generating a population of motor neurons from the skin cells of a patient, he and his colleagues effectively moved the study of ALS "out of the patient and into the petri dish", according to a report in ScienceNOW Daily News.

Eggan and colleagues generated induced pluripotent stem cells (iPS cells) from fibroblasts taken from the skin of an 82-year-old woman with a familial form of ALS. The patient-specific iPS cells behaved like embryonic stem cells and differentiated successfully into motor neurons, the type of cell that ALS destroys.

The patient had a familial form of ALS that occurs in 2 per cent of cases. It is caused by a mutation in a gene called superoxide dismutase 1, or SOD1. 95 per cent of ALS cases however, are sporadic and there is no known inherited mutation, possibly because the genetic change occurs during the person's lifetime through interaction with the environment.

But Eggan was not despondent about this, "I think this approach has incredible promise for studying other forms of ALS," he said, explaining that the symptoms of familial and sporadic ALS are similar and probably share enough common mechanisms to make it worth trying this method with other forms of ALS.

Recent studies have shown it is possible to reprogram human fibroblasts (a type of skin cell that acts like scaffolding and holds other skin cells together) and return them to a "pluripotent state", where they become stem cells that can be coaxed into producing a range of other cells. But this is the first study to show it is possible to do this with the skin cells of an elderly patient with chronic disease.

There are many illnesses that scientists would like to study "outside of the patient", and they hope one day even to be able to grow healthy versions of diseased cells and put them back in the patient. Until recently, it was thought the only way to do this was using the controversial technique of therapeutic cloning, where the DNA of an egg would be replaced with the DNA of the patient, and then the early stage embryo would be harvested for embryonic stem cells that had the same DNA as the patient. The method is yet to be proved in humans though.

However, using induced pluripotent stem (iPS) cells overcomes the ethical problems of using embryos. They are adult cells that are reprogrammed to behave very much like embryonic stem cells. Two years ago, scientists inserted four genes into the skin cells of mice and rats to create iPS cells, and then last year, this was done with human skin cells. And now, with this latest study, it would seem that researchers have taken the method a step further, by showing you can make iPS cells from a chronically sick person's skin cells and turn them into healthy versions of the cells that are being killed by the disease.

For this study, Eggan and colleagues put the same four genes into about 30,000 skin cells taken from the patient. Although hundreds of colonies were cultured, only a handful had the correct markers for pluripotency. These were then coaxed into nerve cells by using molecules that are known to guide mammalian stem cells into nerve cells. Tests showed that a significant proportion of them had markers characteristic of motor neurons, but the final confirmation awaits further tests where the cells are injected into mouse or chick embryos to see if they form the connections characteristic of neurons.