Treating Huntington’s With Gene Knockout Might Be Safe For Adults

Although deleting the huntingtin gene is lethal for young mice, it appears to safely treat the disease in adult mice.

AsianScientist (Mar. 30, 2016) – Huntington’s disease, an incurable neurodegenerative condition, is caused by mutations in the huntingtin (HTT) gene. Previous attempts to treat the disease by deleting the gene in mice have been unsuccessful, as HTT is required during early development.

In a study published in the Proceedings of the National Academy of Sciences, researchers have found a method to selectively deplete huntingtin in the brains of adult mice, thereby opening new avenues to treat Huntington’s disease.

Reducing the expression of mutant HTT is an important strategy for researchers working with mice genetically modified to show symptoms of Huntington’s disease. Considerable efforts have been devoted to developing siRNA and anti-sense oligonucleotides to suppress the expression of mutant HTT in adult brains. Unfortunately, these approaches have also raised concerns that markedly suppressing HTT expression will lead to side effects by impairing HTT’s normal function.

Using conditional HTT knockout mice, the team from the Institute of Genetics and Developmental Biology at the Chinese Academy of Sciences, reported that depleting huntingtin in adult mouse neurons did not trigger Huntington’s-related neurodegeneration or discernible symptoms.

However, loss of huntingtin in two-month-old mice proved lethal, likely due to acute pancreatitis, marked by the loss of pancreatic acinar cells, which undergo degeneration mediated by the digestive enzyme trypsin that is normally kept in check by huntingtin. Expressing a truncated huntingtin protein lacking the N-terminal region in huntingtin-depleted mice reduced pancreatitis and prevented death.

The study suggests that huntingtin might play age- and cell type-specific roles in humans, and the findings point to potential time-sensitive therapeutic gateways for the disease. Furthermore, the results also suggest that depletion of HTT in adults might be an effective therapy.

The article can be found at: Wang et al. (2016) Ablation of Huntingtin in Adult Neurons is Nondeleterious but its Depletion in Young Mice Causes Acute Pancreatitis.


Source: Chinese Academy of Sciences; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Asian Scientist Magazine is an award-winning science and technology magazine that highlights R&D news stories from Asia to a global audience. The magazine is published by Singapore-headquartered Wildtype Media Group.

Related Stories from Asian Scientist