Genome editing used to treat Huntington's disease in mice
Scientists from Emory University in the US have used CRISPR genome editing to alleviate symptoms in a mouse model of Huntington's disease.
Huntington's disease is caused by repeats of the nucleotides CAG in the Huntingtin (HTT) gene. CAG codes for the amino acid glutamine (abbreviated as Q). Huntington's disease and other CAG repeat expansion diseases are therefore also known as polyQ diseases. In this new study, the authors designed guide RNA's to target the Cas9 enzyme to the CAG repeats to permanently cut them out of the HTT gene in striatal neurons. In Huntington's patients, aggregation of mutant huntingtin protein causes these cells die, which leads to neurological symptoms.
The CRISPR strategy in this study reduced the amount of mutant huntingtin protein in the mouse brain. Since the guide RNAs targeted wild type sequence of huntingtin, the amount of wild-type huntingtin protein was also reduced. Although this has been shown to cause problems in young, developing mice, the health of mice older than 4 months followed in this study was not affected. While the mice did not score as well as healthy, wild type mice in motor control, balance and grip strength tests, they clearly performed better than the control Huntington mice. These control mice were treated with a control guide RNA that did not cut out the CAG repeats.
Although there is still a lot of pre-clinical research to be done, the ability to remove the disease causing CAG repeats permanently in specific cells that CRISPR offers, is promising for the future treatment of Huntington's disease.
Digests for a general audience: