Scientists have long struggled to understand how a genetic mutation linked to Huntington’s disease manifests later in life. However, new research has shed light on the process, revealing that the mutation is initially harmless but eventually grows into a larger, toxic version of itself.
A study published in Cell journal found that the genetic mutation associated with Huntington’s disease involves a repeat of the CAG sequence 40 or more times in a specific gene. This initial growth is slow and steady, but accelerates dramatically when the repeats reach around 80. The study also revealed that it’s not just the total number of repeats that matters, but rather when they cross a threshold of about 150.
Once this threshold is reached, certain types of neurons begin to sicken and die, leading to problems with movement, thinking, and behavior. Symptoms typically begin between the ages of 30 and 50, gradually worsening over 10-25 years.
The findings are surprising, even to the researchers themselves, who initially found that repeat expansions in the range of 30-100 CAGs were necessary but not sufficient to cause Huntington’s. The new research suggests that it’s actually when these repeats reach at least 150 that they become toxic.
This discovery has significant implications for the development of treatments and potential prevention strategies. By slowing or stopping the expansion of DNA repeats, researchers hope to target the disease more effectively. While there are no guarantees, the study’s findings have already caught the attention of pharmaceutical companies, which are exploring new approaches to treat Huntington’s disease.
The study’s lead author, Steve McCarroll, noted that “the longer the repeats, the earlier in life the onset will happen.” The research team also acknowledges that more work is needed to understand the complexities of the disease, but this breakthrough brings hope for a better understanding and potential treatment options.
Source: https://phys.org/news/2025-01-huntington-disease-devastating-fatal-brain.html