'The findings open up an avenue for treating Huntington's as well as other inherited neurodegenerative diseases, although more testing of safety and long-term effects is needed,' said Professor Xiao-Jiang Li at Emory University School of Medicine, USA, and senior study author. The work was published in Journal of Clinical Investigation.
Huntington’s disease is a genetic condition caused by a mutant form of the huntingtin gene (mHTT). It produces a toxic protein that accumulates in brain cells and causes progressive cognitive and motor decline, typically in mid-life, eventually leading to death.
The team of researchers used adult mice that contained the human form of the mutant gene, and were already showing signs of the disease. Using CRISPR/Cas9, they introduced genetic changes in an afflicted region of the brain that prevented further production of faulty protein. After three weeks, the mouse brains showed a reduction in the build-up of the mutant protein, and a concomitant improvement in their physical functions - although not to the levels of the control mice.
These observations highlight the ability of brain cells to repair themselves, the researchers believe.
Extending the results to human patients, the authors wrote: 'Thus, reducing mHTT expression in the brains of elder HD patients might still be effective in alleviating neurological symptoms.'
The scientists also sequenced the entire genome of the mice brain cells, which showed that genetic changes had predominantly occurred in the targeted gene. These results follow concerns about the safety and specificity of CRISPR/Cas9 genome editing raised recently, particularly incidences of unwanted mutations and changes in unintended parts of the genome (see BioNews 903).