Gene editing could transform Huntington’s treatment – study

Gene editing has improved movement and reduced harmful protein build-up in mice with Huntington’s disease, according to preclinical research.

Researchers found that shortening repeated sections of DNA associated with the condition improved motor function and restored healthier patterns of gene activity in brain cells.

The findings suggest the technique could offer an alternative to conventional gene editing, although its safety and effectiveness have not been established in humans.

The research, led by Cardiff University, used a modified CRISPR gene-editing approach to target the genetic changes responsible for Huntington’s disease.

Huntington’s is a rare, fatal genetic condition caused by an abnormal expansion of repeated DNA sequences known as CAG repeats.

These sequences can expand over time, contributing to the build-up of toxic proteins and the progression of the disease. There is currently no cure.

Vincent Dion, professor at the UK Dementia Research Institute at Cardiff University and leader of the research team, said shortening these sequences could offer a potential treatment strategy.

He said: “The length of these repeated sequences accounts for most of the variation in how severe the disease is, so targeting and reducing these sequences is a potentially viable therapeutic avenue.”

Conventional gene-editing techniques often cut both strands of DNA to disable mutated genes. However, this can cause unwanted changes, including DNA rearrangements, mutations at unintended locations and damage to healthy copies of genes.

The researchers instead used an enzyme called Cas9 nickase, which cuts only one strand of DNA within the repeated CAG/CTG sequences.

The aim is to shorten the expanded repeats without making the double-strand cuts used in conventional gene editing.

The technique was tested in mouse models of Huntington’s disease, with the gene-editing components packaged into viral vectors, which act as carriers to deliver genetic material into cells.

These were delivered directly to the striatum, a brain region particularly affected by the condition.

The treatment shortened the repeated DNA sequences in most of the targeted neurons, the nerve cells that transmit information within the nervous system.

Researchers also found fewer toxic protein aggregates, abnormal clumps of protein associated with Huntington’s disease.

Dion said: “This led to fewer toxic Huntington protein aggregates, restored healthier gene expression pathways in brain cells, and showed significant improvements in motor function during locomotion tests.”

No unwanted mutations were detected in brain cells from the treated mice.

The researchers believe the findings suggest that cutting a single DNA strand could offer a potentially safer alternative to conventional gene-editing approaches.

However, the results are limited to mouse models, and further research is needed before the technique could be considered for use in humans.

The team says the next steps include improving delivery methods to ensure the gene-editing tools remain active over time without triggering unwanted immune responses.

Researchers also want to investigate whether treatment at an earlier stage of Huntington’s disease could prevent neurological damage before symptoms develop.

More extensive safety and effectiveness testing in larger preclinical models will be needed to establish whether the approach could eventually progress to human clinical trials.

Because the technique targets expanded DNA repeats, it may also have applications in other genetic conditions caused by similar abnormalities.