The disease is caused by a dominant mutation in a gene called HTT which encodes a protein called Huntingtin. In general, humans carry two copies of every gene, but because this disease is "dominant," only a single bad copy of the gene is sufficient to cause disease. The malformed protein which results from this mutation triggers the decay of neurons, and this causes the symptoms associated with the disease.
Scientists researching Huntington's would like to study human cells possessing the mutation, but these can be difficult to obtain. Now, scientists at Johns Hopkins, along with an international team of researchers, have converted skin cells from healthy controls and Huntington's patients into induced pluripotent stem cells (iPSCs) and neurons.
To accomplish this, the researchers extracted fibroblasts (a connective tissue cell) from skin biopsies. They reprogrammed them to become iPSCs by infecting the fibroblasts with a genetically modified virus encoding proteins called transcription factors. Transcription factors selectively activate certain genes, and in the process, reprogram the fibroblasts to an undifferentiated state. (Though similar, iPSCs are not identical to embryonic stem cells.)
To determine if their technique worked, the researchers compared iPSCs derived from normal controls with those derived from Huntington's patients. A series of tests which examined various aspects of gene expression, cellular biology, and metabolism demonstrated that the cell lines derived from Huntington's patients behaved differently from those derived from healthy controls, and the data was consistent with previous Huntington's research. Thus, the authors successfully derived stem cell lines from the skin of patients afflicted with Huntington's disease.
Furthermore, using a cocktail of various growth factors, the authors showed that the iPSCs can be coaxed to grow into neuronal stem cells, and finally, into neurons.
Hopefully, these iPSCs and neurons will allow for faster screening of potential therapies and will expedite Huntington's disease research.
Source: The HD iPSC Consortium, Induced Pluripotent Stem Cells from Patients with Huntington's Disease Show CAG- Repeat-Expansion-Associated Phenotypes, Cell Stem Cell (2012), http://dx.doi.org/10.1016/j.stem.2012.04.027
(Diagram: An example of a family pedigree depicting the inheritance of an autosomal dominant trait. Credit: Jerome Walker/Wikimedia Commons)