Fight against Huntington's disease: hope through Bochum's research!

Fight against Huntington's disease: hope through Bochum's research!

Huntington's disease is a devastating genetic neurodegenerative disease that affects around 1 in 10,000 people in Germany. This latent threat is caused by an autosomal dominant mutation in the huntingtin gene, characterized by the expansion of CAG repeats in exon 1. We owe much of our insight into this complex disease to the research of Nancy Wexler. Wexler, a neuropsychologist who herself lost several family members to Huntington's disease, collected blood samples from those affected in the Lake Maracaibo area of ​​Venezuela in 1981. This pioneering work led to the discovery in 1993 of the responsible gene on chromosome 4, which can now be diagnosed with 100% certainty news.rub.de reports.

Despite the possibility of genetic testing, most people worldwide choose not to undergo genetic testing. Only about 20% can be tested, even if one parent is a carrier of the mutated gene. This is often due to the associated stigma and fears surrounding the disease, which progresses to death over 15 to 20 years. The director of the Huntington Center NRW, Prof. Dr. Huu Phuc Nguyen from Bochum addresses these challenges and supports destigmatization initiatives such as “Hidden no more”, which was launched by Pope Francis in 2017. At an audience in Rome, 2,000 people affected by HD were invited to promote their visibility.

Research and therapeutic approaches

Research into curing the disease has become increasingly important in recent years. There are currently 14 global trials testing potential therapies, including gene therapy approaches. A promising technology is antisense oligonucleotides (ASOs), which are being tested in clinical trials. Tominersen, one such ASO, has already been extensively studied and showed a dose-dependent reduction in mutant huntingtin. However, patients reported undesirable side effects, such as disturbances in cerebrospinal fluid circulation. Another ASO, WVE-003, targets specific polymorphisms and is also being tested, while the miRNA AMT-130 represents a promising possibility to reduce the synthesis of huntingtin.

Various approaches, such as the use of splicing modulators and zinc finger proteins, are also being developed. Research has shown that the length of CAG repeats is critical to disease progression. People with over 35 CAG repeats are at increased risk of developing the disease; if the number is 40 or more, the outbreak is certain within a lifetime. The challenge remains, however, that there is currently no causal therapy. Existing symptomatic treatments focus primarily on movement disorders without addressing the underlying cause, such as pmc.ncbi.nlm.nih.gov highlights.

Outlook for the HD community

Developments in research give hope for patients and their families. The findings from the “GENERATION HD1” study were considered disappointing; however, they provided valuable information for future studies. Biomarkers such as neurofilaments could potentially contribute to early diagnosis and monitoring the progression of the disease. Wexler's influence remains unwavering: her commitment has contributed not only to scientific education, but also to promoting the visibility of the HD community.

When considering the challenges and advances in research, it is clear that Huntington's disease still poses many unanswered questions. It remains one of the most significant challenges in neurological medicine, while innovative approaches to treatment and cure are continually being investigated.