Genetic Modifiers, CSF Flow, and Sleep in HD

HD Buzz on Genetic Modifiers in HD 

People with an expanded section of CAG repeats in a copy their huntingtin gene will develop Huntington’s disease, but people with the same numbers of CAG repeats will not necessarily develop symptoms at the same time. Genetic modifiers of HD can affect how slowly or quickly HD will progress a person with an expanded huntingtin gene, and some of these modifying genes code proteins focused on cleaning up mistakes in the way DNA is copied—DNA mismatch repair proteins. Understanding the relationship between these genes and their influence on disease progression could inform treatments to delay onset of the disease. A recent study published by researchers at Thomas Jefferson University reveals new details about how these modifiers work; read the HD Buzz breakdown on the highlights, here.  

How does CSF flow change in HD?  

Cerebrospinal fluid (CSF) is an important part of the Central Nervous System (CNS); it bathes the brain and spinal cord, protects them, and facilitates communication between the CNS and the rest of the body. CSF can be accessed by a spinal tap, which is a possible site of administration for HTT-lowering drugs, as it allows them to be administered directly into the CNS. But research has shown that this method of administration results in limited distribution in brain tissue.  

2022 HDSA Human Biology Project Fellow, Dr. Kilian Hett, is studying why this may be. CSF flow gets slower as people age, but a recently published paper detailing Kilian’s findings indicated that CSF flow may be further altered by HD. Dr. Hett used a special type of imaging to assess CSF flow in people at different stages of HD and found that the further someone’s HD symptoms have progressed HD, the slower the flow of their CSF. This could be one reason mutant huntingtin protein builds up in the brain and CNS over time—the body’s natural system of removing it is impaired. These findings may also be important for developing best practices of administering HD drugs via spinal tap for people with HD to maximize their efficacy. To read the full article, click here.  

Sleep in HD: A special edition of the Journal of Huntington’s Disease 

We all know that sleep is an important part of living a healthy lifestyle, but why is sleep important for people with HD, and how might sleep be disrupted by the disease? The most recent issue of the Journal of Huntington’s Disease focuses on what we do know about sleep in HD, as well as what we still need to find out. Highlights include a clinician’s perspective on sleep in HD based on her experiences treating people with the disease, how different HD drugs may impact sleep, and perspectives on sleep from HD family member and advocate, Alice Wexler. This special edition on sleep is entirely open access, which means it is available to the public for free. Read more here.