KEY POINTS
- The mutation of the huntingtin gene (HTT) becomes toxic when CAG repeats exceed 150.
- This expansion of repeats gradually kills striatal neurons, which are crucial for various functions including cognition, motor skills, and behavior.
- Researchers hope this study will lead to new therapies to slow down and prevent the disease.
In France, approximately 18,000 individuals are affected by Huntington’s disease, according to the National Institute of Health and Medical Research (Inserm). Among these, around 6,000 exhibit symptoms, while the remaining are asymptomatic carriers of the hereditary mutation of the huntingtin gene (HTT). This mutation is the root cause of the disease, leading to the death of brain cells.
huntington’s Disease Affects Striatal Neurons at 150 CAG repeats
“Typically, this gene [HTT] contains a sequence of 35 repeats of a nucleotide triplet (CAG), which codes for the amino acid glutamine,” as noted by Inserm. “Though, in Huntington’s disease, an abnormal number of these triplet repeats is observed. Generally, the greater the number of repeats, the earlier the onset of the disease.”
Until now, scientists were uncertain about how this mutation led to the death of brain cells. However, a recent study published in the journal Cell provides clarity. Researchers have uncovered the mechanism by which this hereditary genetic mutation causes cell death.
recent research has shed new light on the genetic mechanisms underlying Huntington’s disease, especially focusing on the impact of CAG repeat sequences in the HTT gene. A study involving brain tissue analysis from 53 individuals diagnosed with Huntington’s disease, alongside 50 healthy controls, has revealed significant findings regarding the health of striatal neurons, which are crucial for cognitive, motor, and behavioral functions.
Historically, most studies have concentrated on CAG sequences of fewer than 100 repeats. Though, this new research has identified instances where some neurons exhibited up to 800 CAG repeats. Notably, the transition from 40 to 150 CAG repeats did not appear to adversely affect neuronal health. It is only beyond the threshold of 150 CAG repeats that these neurons began to show signs of deformation and eventual cell death.
The study further elucidates the timeline of this genetic mutation’s progression.It typically takes several decades for the CAG repeat count to reach 80. Following this, the rate of expansion accelerates dramatically, reaching 150 CAG repeats within just a few years. Onc this critical point is surpassed,the striatal neurons begin to die off. This indicates that for approximately 95% of the lifespan of these neurons, the HTT gene mutation remains relatively harmless. Though,it gradually evolves into a highly toxic form that leads to rapid cell death.
These findings not only enhance our understanding of Huntington’s disease but also open avenues for potential therapeutic interventions aimed at mitigating the effects of this devastating condition. As researchers continue to explore the complexities of genetic mutations, the hope is to develop strategies that can delay or prevent the onset of symptoms in affected individuals.
New Insights into Potential Treatments for Huntington’s Disease
Recent research has shed light on Huntington’s disease, a genetic disorder that has long puzzled scientists. “we already knew a lot about Huntington’s disease before starting this work, but there were gaps and inconsistencies in our collective understanding,” said a key researcher involved in the study. The team has successfully mapped the complete trajectory of the disease within neurons over decades, revealing numerous potential intervention points for therapeutic strategies.
Currently, Huntington’s disease remains an incurable condition. Though, this groundbreaking revelation opens the door to the progress of new therapies. Rather than solely targeting the HTT gene, researchers are exploring innovative approaches that could slow down or halt the increase of CAG repeats, which are linked to the progression of the disease.
Discussion between the Time.news Editor and an Expert on Huntington’s Disease
Time.news Editor: Thank you for joining us today too discuss the recent findings on Huntington’s disease. One of the key points that stood out is that the mutation of the huntingtin gene (HTT) becomes toxic when CAG repeats exceed 150. Can you explain how these repeats lead to the neurodegeneration seen in this condition?
Expert: absolutely, and thank you for having me. The huntingtin gene typically has around 35 CAG repeats, which is considered normal. However, when the number of repeats goes beyond 150, the resultant protein produced becomes misfolded and toxic to neurons, especially those in the striatum. This region of the brain is critical for various functions, including coordination of movement and cognitive processes. The toxicity from the mutated protein causes progressive cell death, leading to the symptoms associated with huntington’s disease.
Time.news Editor: That’s alarming. In France alone, we know approximately 18,000 people are affected, with around 6,000 showing symptoms. How do researchers hope to address this issue with the current knowledge on the CAG repeat expansion?
Expert: The focus of current research is to understand the mechanisms through which these toxic proteins harm neurons. By targeting the molecular pathways involved, scientists hope to develop therapies that can either slow down the progression of the disease or perhaps even prevent it altogether.Recent studies have shown promise in avenues like gene editing and the use of small molecules that can interfere with the toxic effects of the mutant huntingtin protein.
Time.news Editor: That sounds promising. The idea of new therapies could change the lives of those affected. Can you share any specific therapeutic approaches that are currently being researched or tested in clinical trials?
Expert: Certainly! One strategy includes the use of RNA-targeting therapies that aim to reduce the levels of the mutant huntingtin protein in the brain. For instance, recent trials have explored antisense oligonucleotides—short DNA molecules designed to bind to the mutant mRNA and mark it for degradation. This could possibly lower the overall production of the toxic protein. Additionally, some researchers are investigating the benefits of stem cell therapies to repair or replace damaged neurons in the striatum.
Time.news Editor: It’s captivating to see how advancements in genetics and biotechnology are paving the way for innovative treatments. As researchers make progress, what role do you think public awareness and support play in tackling diseases like Huntington’s?
Expert: Public awareness is crucial. It can foster understanding and empathy toward those affected, drive funding for research, and encourage participation in clinical trials. Advocacy groups can also help in raising awareness about genetic testing options for at-risk individuals, which can lead to earlier interventions and better management of the disease. the more people understand Huntington’s disease, the more likely we are to see advances in both research and support systems.
Time.news Editor: Thank you for shedding light on this important topic. It’s clear that while Huntington’s disease remains a important challenge, the ongoing research holds great promise for future therapies that could enhance the quality of life for those affected. We look forward to following your work and will keep our readers updated on developments in this field.
Expert: Thank you for the chance to discuss this, and I share your hope for future advancements. Appreciate your commitment to covering such critical health issues!