Huntington's disease (HD) affects about 1 in 10,000 people in America, and about 1 in 8500 in the UK. Symptoms usually start to manifest in middle age and include uncontrolled movements, emotional and cognitive deterioration, and eventually, dementia and death.
HD is caused by a triplet expansion in the Huntingtin (HTT) gene, resulting in a protein that does not function properly.
Healthy people have between 7 and 35 CAG repeats near the start of the gene, whereas affected individuals have 36 or more. The greater the expansion, the more severe the symptoms. Instead of folding properly, the mutated proteins start to stick together, disrupting how the cell works. This has dire consequences in the brain, with the aggregation of the protein eventually killing the cells.
HD is an autosomal-dominant disease, meaning that only one bad copy of the gene needs to be inherited from a parent (or mutated spontaneously) for an individual to be affected, even if the other copy is perfectly fine.
One potential way to prevent the disease manifesting is to knock out the affected copy and stop it working at all, but this is difficult without accidentally the targeting the normal copy as well.
A recent paper published in Human Molecular Genetics by Jun Wan Shin et al has tackled this problem by using CRISPR/Cas9 technology. Instead of trying to remove the extra triplets, which would be very difficult, they scanned the genome sequence within the HTT gene to look for natural variation that could work to their advantage. By studying the haplotypes (a group of variants inherited together) of affected and normal individuals, they discovered a series of single base mutations that were present in the disease chromosomes but not healthy ones.
Taking one haplotype to study further, they designed guide RNAs to target these variations specifically, and instruct Cas9 to cut only at the affected chromosome and leave the normal one intact. The experiments were performed in human fibroblast cells, isolated from an affected patient and grown in culture.
The cuts resulted in a deletion of 44,000 base pairs at the beginning of the gene, including the promoter and transcription start site, which stopped the gene making any protein at all. The healthy chromosome continued to make a normal protein, unaffected by the gene editing activity on the mutant gene.
Although we are still many years away from a gene therapy solution to Huntington's Disease, these breakthroughs offer a path for real treatments the future
 Shin, J. W., Kim, K.-H., Chao, M. J., Atwal, R. S., Gillis, T., MacDonald, M. E., … Lee, J.-M. (2016). Permanent inactivation of Huntington’s disease mutation by personalized allele-specific CRISPR/Cas9. Human Molecular Genetics, ddw286. https://doi.org/10.1093/hmg/ddw286