The age that Huntington’s disease symptoms appear can vary a lot from person to person. For decades, scientists have been exploring the reasons behind this, and an important new finding has recently emerged. The vast majority of people with HD have a certain type of genetic “hiccup” near the end of their CAG repeat – one CAA. This doesn’t actually change the huntingtin protein, so we didn’t know it was important until now. Very rarely, this CAA hiccup occurs twice (for about 1 in 100 people with HD). In these individuals, symptoms tend to occur later in life. Even more rarely, the CAA hiccup is absent (for about 1 in 300 people with HD). For these individuals, symptoms tend to occur earlier. This discovery was made simultaneously by two separate research groups working with data from more than 9,000 individuals with HD, and formally published this month. 

This is not something that a doctor could test for – such spelling differences in the HD gene are extremely rare, so today’s genetic tests are not designed to pick it up. However, to many HD researchers, this discovery about the CAA hiccup feels like fitting in a missing puzzle piece. HDBuzz explained in detail back in March. A few years ago, there was a major HD discovery suggesting that the body’s ability to repair damaged DNA could contribute to age of onset, and this finding helps to confirm that hypothesis.


This Week in HD History: Observational Research Studies

August of 2002 marked the beginning of an important observational study called PREDICT-HD. Based in Iowa, it was one of the largest early studies to track the development of HD symptoms in thousands of individuals over time, and the data is still being used to better understand early HD. In fact, if you live near the University of Iowa or are interested in traveling to participate, PREDICT-HD 3.0 has recently launched and will continue to build on this work.  

Large observational studies are becoming more and more important because the knowledge gained helps to build a case for testing drugs in people with the HD gene before symptoms begin. Studies like Enroll-HD are also magnets for pharma companies to study HD and to recruit individuals who are already participating in research. That’s why HDSA highly encourages participation!