ALS Stem Cell Breakthrough

[Guest guest]

http://www.medicalnewstoday.com/articles/117006.php

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 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.

Rothstein of s Hopkins University in Baltimore, land,

a stem cell researcher who is also studying ALS, told ScienceNOW Daily

News that: " It is exciting that they have generated human cells from

the patient material. "

But he suggested that there is still a long way to go, because the

cells are only useful if they are exactly the same as the ones causing

the disease in the patient, partial replicates would be of little use,

and it is important to bear in mind that iPS generated cells are quite

different to cells buffeted by a lifetime of drugs and other

environmental and metabolic influences.