A new way to treat Huntington’s disease . This is what a team of researchers from Emory University in Atlanta (USA) and the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences (China) have achieved, after managing to ‘interrupt’ the mutation in the huntingtin gene using the ‘CRISPR / Cas9’ gene editing technique , popularly known as the genetic ‘cutter’, which allows genes to be deleted, added or changed at will. The discovery, which has been successfully tested in mice, has been published in the Journal of Clinical Investigation.
Scientists have managed to correct this mutation, remove the aggregates, and reverse both the disease and the motor symptoms. Will this technique work for humans? So far, it has worked in mice and opens a hopeful way to treat these and other inherited neurodegenerative diseases such as amyotrophic lateral sclerosis, Parkinson’s disease, Friedreich’s a taxia or Alzheimer’s disease.
For their experiment, the researchers used an animal model – mice – which they genetically engineered to contain the mutant huntingtin gene that causes the disease in humans. Thus, when the rodents had reached 9 months of age, the protein formed aggregates in the brain and began to show the characteristic motor problems of the disease. At that time, they injected an adeno-associated virus – similar to that of colds – with the CRISPR / Cas9 sequence with the guide RNA for the mutated huntingtin gene into the striatum of the brain of the mice with the intention of cutting out part of this gene that produces toxic protein aggregates in the brain.
The results were astonishingly fast. In just 3 weeks, the treatment had managed to dramatically reduce the aggregates of the defective protein in that brain area – they had almost disappeared – and the mice had incredible motor control and balance.
Specifically, compared to Huntington’s control mice, the CRISPR / Cas9-injected mice showed significant improvements in tests of motor control, balance and grip strength, although they were not at the level of the control group mice.
On genetic safety concerns, the researchers showed that the CRISPR / Cas9-activated switch mutations occurred predominantly within the huntingtin gene and not in other potential genes. However, the long-term effects and safety of using this technique in the human brain to express CRISPR / Cas9 will have to be rigorously tested before applying this approach to patients.
Reference: Su Yang et al, CRISPR / Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington’s disease, Journal of Clinical Investigation (2017). DOI: 10.1172 / JCI92087
