2024 Human Biology Project Launch, HD History, The Buzz on CAG’s

HDSA Launches 2024 HD Human Biology Project Letter of Intent 

HDSA is proud to announce the 2024 Request for Proposals for the HD Human Biology Project. Despite the identification of the gene responsible for Huntington’s disease (HD) over 30 years ago, there is not yet an effective treatment to slow or stop the progression of symptoms. While remarkable advances in HD biology have been made using animal models, the development of effective therapies requires research in humans. As a result, HDSA has adopted a human-centric research strategy to push the HD field closer to slowing progression and onset. HDSA’s HD Human Biology Project is the cornerstone of this strategy, with the aim of better understanding the biology of Huntington’s disease as it occurs in humans. This one-to-two-year funding mechanism is open to researchers around the world and provides up to $90,000 of annual support for research conducted in collaboration with HD clinics across the globe. To learn more, click here.   

This Week in HD History 

We’ve known since 1993 that a CAG-repeat expansion in the huntingtin gene leads to Huntington’s disease. This discovery paved the way for numerous transformative studies to further HD science.  
 
In March of 2000, scientists from Columbia University published a mouse model of HD in which expression of expanded huntingtin proteins produced from the HD-causing gene could be switched on and off. When mutant huntingtin protein was produced, the mice experienced symptoms of HD, but when production of mutant huntingtin was blocked in those same mice, their symptoms of HD subsided. This research was some of the first to support the hypothesis that lowering of mutant huntingtin protein could stop or slow the symptoms of HD.  
 
While the presence of expanded huntingtin protein was linked to HD symptoms, onset is variable. Though the CAG repeat length is a major disease driver, a variety of additional genetic and environmental factors can influence when HD symptoms begin. This idea gained strong scientific support in March of 2004, when a consortium of researchers led by Dr. Nancy Wexler published a paper confirming that HD onset is unpredictable and depends on both genetics and lifestyle. This determination was made with the amazing contribution of data and samples from thousands of willing participants living along the shores of Lake Maracaibo in Venezuela, an incredible collaboration between scientists and HD families that has fueled discoveries about HD for decades since.  

The Buzz on CAG-repeat expansion 

HD is one of several diseases related to an elongated stretch of C-A-G’s in DNA. Understanding this phenomenon could uncover why cells get sick in HD and related diseases, and why some types of cells are affected more than others. This may lead to new treatment options that keep cells healthier for longer and keep symptoms at bay. A group of scientists in Massachusetts are studying why CAG-repeat expansion leads to production of harmful proteins, and how this harms cells. HD Buzz covered their findings and what they mean for CAG repeat expansion diseases in their most recent article—read it here.