Huntington's disease in vitro
Novosibirsk geneticists create a cellular model of Huntington's disease
Scientists of the FITZ Institute of Cytology and Genetics and the Institute of Chemical Biology and Fundamental Medicine SB RAS use gene editing methods to create a cellular model of Huntington's disease.
The study of molecular processes underlying neurodegenerative diseases is an urgent direction of modern biomedicine. In particular, scientists are studying the selective death of striatum neurons (the structure of the anterior part of the brain) in Huntington's disease. This genetic pathology is associated with an increase in the expansion of nucleotide repeats: the fact is that the HTT gene encoding the huntingtin protein normally contains from 8 to 36 CAG repeats (sequences of nitrogenous bases cytosine-adenine-guanine), but with this disease their number increases to 37-80. Such a mutant gene leads to the synthesis of mutant huntingtin, which forms protein aggregates in striatum neurons and thereby has a toxic effect on these cells, which leads to their further death – this is how the disease develops.
– Despite the fact that the mutation was detected more than 20 years ago, there are still no effective methods of treatment or at least slowing down the disease, so the urgent task is to create its cellular models on which it will be possible to test drugs and study molecular mechanisms of pathogenesis at the cellular level, – said at the conference "Biotechnology – medicine future" graduate student of Novosibirsk State University Tuyana Malankhanova.
Induced Pluripotent Stem Cell (IPSC) technologies they just provide a platform for research of this kind, since these cells can be differentiated into different types of cells, including the middle spike neurons of the striatum, which die in Huntington's disease. In addition, it is possible to create and study cellular models using gene editing methods.
One of the directions of using gene editing is the creation of isogenic disease lines. Usually, patient-specific cells are used as a cell model, and cells of a conditionally healthy person are used as a healthy negative control, but this is not the best option. The fact is that all people differ greatly in the presence of millions of polymorphisms, which means that the results of studies on such pairs of cells may not be completely adequate. That is why scientists are faced with the task of obtaining isogenic pairs of lines, that is, pairs where cells have the same genetic background and differ only in the mutation that causes the disease.
There are two ways to create these lines: either to correct mutations in the patient's cells, or, conversely, to introduce the corresponding mutations into healthy ones. Siberian researchers use the second option, as this allows us to obtain an entire panel of several different lines carrying different numbers of CAG repeats in the HTT gene.
– The creation of cellular models is an actual trend, and the most important thing is the creation of accurate models that will fully or as accurately as possible reflect the processes in the cells of the human body, – summed up Tuyana Malankhanova.
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27.07.2017