Wednesday, 07 December 2011 21:36

Hereditary nerve disease investigated with the help of iPS Featured

The Life & Brain research centre led by the stem cell researcher Prof. Dr. Oliver Brüstle from Bonn, Germany, and the German Centre for Neurogenerative Diseases (DZNE) have successfully applied in vitro methods with the help of induced pluripotent stem cells to unlock the secret to the Machado-Joseph disease, a hereditary movement coordination disorder.

To study the disease, the researchers derived induced pluripotent stem cells (iPS cells) from small samples of skin from patients with Machado-Joseph disease. They then converted the iPS cells into brain stem cells, creating an ever-ready supply of neurons for their investigations. The cause of the disorder is a repeating sequence in the ATXN3 gene, which causes a build-up of the Ataxin protein, damaging neurons in the brain. This genome sequence was present in the patients’ cells and therefore also in the iPS cells.

The engineered nerve cells were stimulated using electrical currents. The researchers were able to determine that the formation of the harmful protein aggregates is directly related with a neuron’s electrical activity. A key role is played by an enzyme called calpain, which is activated by increased calcium levels in the nerve cells when stimulated by the electrical current.


Abstract: Koch, P., Breuer, P., Peitz, M., Jungverdorben, J., Kesavan, J., Poppe, D., Doerr, J., Ladewig, J., Mertens, J., Tüting, T., Hoffmann, P., Klockgether, T., Evert, B. O., Wüllner, U. & Brüstle, O. (2011): Excitation-induced ataxin-3 aggregation in neurons from patients with Machado–Joseph disease. Nature (Vorabveröffentlichung doi:10.1038/nature10671).