Genetic disease 'created in lab'

Newspapers report today that researchers have recreated a genetic disease in a laboratory. The Times said that scientists created stem cells and nerve cells with characteristics of spinal muscular atrophy using skin cells from a child with the most severe form of the genetic condition. This enabled them to observe its early progress, which could eventually lead to new therapies to treat this condition.

This important study illustrates the rapid advances being made in stem cell research. Prior to this, researchers have had to rely on animal models of the condition to study this disease. These models are limited by the fact that they may not accurately reflect what happens in the human body.

The practical application of this early research is to give researchers a more accurate model through which to test potential treatments.

Where did the story come from?

Alison Ebert from the Waisman Center and The Stem Cell and Regenerative Medicine Center, with colleagues from other departments at the University of Wisconsin-Madison in the US, conducted this research. The work was funded by grants from the Amyotrophic Lateral Sclerosis Association and National Institutes based in the US. It was published online in the peer-reviewed science journal Nature .

What kind of scientific study was this?

In this laboratory study, the researchers wanted to see if they could use a type of stem cell to model the specific pathology of spinal muscular atrophy, a genetically inherited disease.

Human stem cells can come from different sources, such as embryos or the umbilical blood. The stem cells that were examined in this study, human induced pluripotent stem cells, are different in that they can be derived from developed cells such as skin cells. These can be 'induced', or forced, to take on some of the characteristics of stem cells, such as the ability to become specialised nerve cells.

The researchers say that fibrous skin cells (fibroblasts) have already been used extensively in studying spinal muscular atrophy. They felt, however, that as the nerve cells that control muscles are unique, they could better study the disease process by developing a technique of producing these nerve cells from the pluripotent stem cells from fibroblasts.

Spinal muscular atrophy is a commonly inherited neurological disease with a range of severities. Children with it begin to lose nerve cells outside the brain (for example in the spinal cord), which leads to progressive muscle weakness, paralysis and often death.

The cause of the disease has been tracked back to mutations of genes on chromosome 5, the SMN1 or SMN2 genes. In order for a child to have the condition, they must inherit two copies of the defective genes. As yet there is no known cure, though the protein produced by this gene has been identified.

In this research, the scientists took a sample of fibrous skin cells from a child with spinal muscular atrophy. They succeeded in producing pluripotent stem cells from these, which were then grown further until they divided and finally changed into nerve cells. When they analysed the genes in the nerve cells, they found the same selective deficits as found in the child's unaffected mother.

What were the results of the study?

The researchers claim to be the first to have used human induced pluripotent stem cells to demonstrate the changes in cell survival or function typical of this disease. They report that they grew stem cells from both the affected child (with two defective genes) and from his unaffected mother (with only one gene), and showed that these cells could develop into nerve tissue and motor nerve cells. The cells retained the gene defect, a lack of the gene SMN1 expression, and the cells eventually died in a way that was typical for the disease.

What interpretations did the researchers draw from these results?

The researchers conclude that their main results, “will allow disease modelling and drug screening for spinal muscular atrophy in a far more relevant system”. In other words, using a disease model that more closely resembles what actually happens in humans.

They claim that “this is the first study to show that human induced pluripotent stem cells can be used to model… a genetically inherited disease.” They say their research is important because it provides a new way of studying how diseases develop. This could lead to early ways of testing new drug compounds, which in turn may lead to the development of new therapies.

What does the NHS Knowledge Service make of this study?

This important study illustrates the rapid advances being made in stem cell research. Although there are animal models of spinal muscular atrophy in mice, flies and worms that can be made to model a similar disease state, they are limited as they are only models and they are not in human cells. Research that used this new technique would be more likely to accurately reflect what would happen in a human body.

In addition, as this study used human cell culture that did not come from animals or human embryos, it avoids some of the ethical issues related to this sort of research.