Huntington's disease can be studied "in vitro"
Huntington's disease is a severe hereditary neurodegenerative disease, the symptoms of which usually first appear after 30 years. (However, this may also occur in childhood, as in the case of the patient who provided the material for this study.) The disease manifests itself by sudden involuntary movements, loss of control over muscle movements, mental disorders, dementia and, ultimately, leads to the death of the patient.The cause of Huntington's disease is a mutation of the HTT gene encoding the huntingtin protein. It leads to the synthesis of an abnormal toxic version of the protein. Despite the fact that all the cells of a patient with Huntington's disease have this mutation, toxic huntingtin has its detrimental effect mainly on the middle spiny neurons of the striatum – the region of the basal ganglia of the brain that coordinates movements, thoughts and emotions. Until now, studies on Huntington's disease have been conducted on mouse models. Despite the fact that this made it possible to understand some aspects of the development and progression of the disease, experts believe that the optimal object for its study is the culture of human medium spiny neurons.
In order to create such a culture, the laboratories of Johns Hopkins University, the University of Wisconsin, Massachusetts General Hospital, Harvard University, the University of California, Cardiff University and the University of Milan have joined together in a consortium funded by the National Institute of Neurological Diseases and Stroke of the USA and the non-profit CHDI Foundation.
As part of a joint study, scientists from Johns Hopkins University, working under the guidance of Professor Christopher A. Ross, took a skin biopsy of a 7-year-old patient with an exceptionally early onset of severe Huntington's disease. The cells were cultured under laboratory conditions, after which they were transformed into induced pluripotent stem cells (iPSCs). In parallel, with the help of similar techniques, a control line of iPSC was created from skin cells of a person who does not suffer from Huntington's disease. At the same time, similar pairs of cultures were created from isolated cells by other members of the consortium.
Within three months, the specialists of all the laboratories included in the consortium turned iPSCs into ordinary neurons, after which they turned into medium spike neurons. The neurons obtained from the cells of a patient with Huntington's disease behaved as the researchers expected. They showed rapid degeneration when cultured in a base medium that did not contain special nutritional additives. The neuron lines cultured in parallel under similar conditions, obtained from healthy human cells, had no signs of degeneration.
Inspired by the success, researchers are currently testing the ability of various small molecules to block the process of neurodegeneration occurring in Huntington's disease. They hope to find compounds that could become the active ingredients of new drugs for the treatment of this disease. They also note that cell lines can be obtained in a similar way to study other neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.
The article The HD iPSC Consortium Induced Pluripotent Stem Cells from Patients with Huntington's Disease Show CAG-Repeat-Expansion-Associated Phenotypes is published in the journal Cell Stem Cell.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru Based on Medical News Today: Brain Cells Derived From Skin Cells For Huntington's Research.
28.06.2012