The research expands on what was previously understood about the role of repeated DNA sequences in Huntington's disease.
The findings of the study, conducted by scientists from Cardiff University in the UK, are published in the journal Cell.
"Our findings may not be able to help those already affected by Huntington's disease, but this could prove to be a turning point in how we treat the disease in future generations," states study author Lesley Jones, a professor of neurogenetics at the Institute of Psychological Medicine and Clinical Neurosciences.
Huntington's disease is an inherited degenerative brain disorder that affects movement and cognitive function and can also lead to changes in behavior and personality.
People with the condition inherit a single defective gene. The gene in question, HTT, has a mutation involving a DNA segment known as CAG, comprised of the compounds cytosine, adenine and guanine appearing multiple times in a row.
In most people, the CAG segment is repeated around 10-35 times, but in people carrying the defective HTT gene, the segment is repeated over 36 times. While people with 36-39 CAG repeats may or may not develop Huntington's disease, people who have 40 or more CAG segment repeats in the HTT gene almost always develop the condition.
"We have known for over 20 years that the number of times a certain sequence of DNA repeats itself plays a part in the age at which the symptoms of Huntington's disease develop," states Prof. Jones. "This research goes a step further, and tells us that the way that repeated sequences of DNA are handled by brain cells is likely to be critical in Huntington's disease."
The role of DNA repair in Huntington's disease
For the study, Prof. Jones and colleagues set out to compare the age of onset and the DNA of more than 6,000 patients with Huntington's disease. In doing so, they discovered that the mechanism controlling the manufacture and repair of DNA could influence the age at which individuals begin to develop the condition.
Fast facts about Huntington's disease
- Signs and symptoms of Huntington's disease typically develop when patients are in their 30s or 40s
- Individuals only need to inherit one copy of the defective Huntington gene to develop the disorder
- Adults with Huntington's disease tend to live for 15-20 years following the first onset of symptoms.
Whenever DNA in any cell is repaired, it must be cut so that the incorrect sequence can be removed. The researchers know that the proteins involved with DNA repair lead to CAG segments getting longer in HTT.
Prof. Jones told Medical News Today the team thinks that "DNA repair probably has a role in Huntington's disease through increasing the likelihood of the DNA near the CAG repeat being cut and needing to be repaired. She then explained why the DNA repair mechanism might influence the age of Huntington's disease onset:
"When it is repaired the molecular machinery finds it hard to know the correct repeat length and the CAG repeat gets longer. A longer repeat makes cells more likely to die - so the more this happens, the earlier someone is likely to get the disease."
The researchers believe their findings could lead to further discoveries relating to the development of other diseases inherited through the passing of a single gene, as well as potential ways to treat the currently untreatable Huntington's disease.
"In understanding the mechanisms by which nature influences the age of onset of this devastating condition, we have identified a target for potential treatments," Prof. Jones concludes. "If we can develop a way to interfere with these processes, then we could possibly delay or even prevent the onset of the disease."
Last month, MNT reported on a study that confirmed an activating protein called Rhes plays a pivotal role in Huntington's disease. This protein could become a drug target in future treatments.