Weekly Spotlight - 03.10.24

In the News

Maureen Wins Carer of the Year Award

Congratulations to Maureen, the founder of the Hampshire and Isle of Wight branch, for winning the Carer of the Year Award at the BBC Make a Difference Awards in the Solent region. Maureen has shown extraordinary dedication, caring for her husband, son, and daughter, all of whom had Huntington's disease, and now her grandson who also has the condition. Maureen remains an active committee member and a pillar of the Huntington's disease community. Her tireless efforts across generations have rightfully earned her this recognition. From everyone at the Huntington's Disease Association, we extend our heartfelt congratulations to Maureen for her well-deserved award.

14 Changes for a Healthier Brain

The 2024 Lancet Commission highlights 14 modifiable risk factors for dementia, offering hope for improved brain health. Key factors include education, hearing loss, hypertension, exercise, diabetes, social contact, alcohol consumption, air quality, smoking, obesity, traumatic brain injury, depression, vision loss, and high LDL cholesterol. Addressing these can reduce dementia cases by varying percentages. Encouragingly, even those with genetic risks for dementia or Huntington's disease (HD) can benefit from lifestyle changes. The report underscores the importance of early education, mental health support, and healthy living. While each factor individually contributes modestly, collectively they significantly lower dementia risk, promoting a healthier, longer life.

Neurocrine Biosciences Shows Promising Results for Huntington's Disease Treatment

Neurocrine Biosciences has shared promising interim data from the KINECT-HD2 study, showing significant and sustained improvements in chorea associated with Huntington's disease through Week 104. The study, which includes patients on antipsychotic medication, highlights the long-term safety and efficacy of INGREZZA (valbenazine) capsules. Key findings include: Improvements in chorea observed as early as Week 2, sustained through Week 104. Consistent benefits regardless of antipsychotic use. Over 75% of participants reported significant symptom improvement by Week 104. These results, presented at the 2024 MDS International Congress, offer hope for those affected by Huntington's disease, underscoring the potential of INGREZZA to enhance quality of life.

Understanding Huntington's Disease: Brain and Blood Vessel Impact

Huntington's disease, a genetic condition leading to dementia, affects both nerve cells and microscopic blood vessels in the brain. Research shows these vascular changes occur even before symptoms appear, offering potential for early prediction and treatment evaluation. The study, conducted by Lancaster University and other institutions, used non-invasive techniques to measure brain blood oxygenation and neuronal activity. Findings suggest that monitoring these factors could help track disease progression and assess the impact of treatments or lifestyle changes. Professor Aneta Stefanovska hopes this research will inspire new treatments targeting brain vasculature and metabolism.

Compensatory Astrocyte State in Huntington's Disease Uncovered

The study "Multi-omic analysis of Huntington's disease reveals a compensatory astrocyte state" uncovers significant findings about the role of astrocytes in Huntington's disease (HD). Researchers used advanced techniques like single-nucleus and bulk RNA sequencing, lipidomics, and immunofluorescence to analyse post-mortem brains from HD patients and controls. They discovered that certain astrocytic states, particularly those rich in metallothioneins, play a crucial role in protecting neurons from degeneration. This compensatory state was notably present in less affected brain regions, suggesting potential therapeutic targets. Key findings include: Identification of genes correlated with CAG repeat length, enriched in astrocyte genes. Discovery of lipidomic signatures implicating poly-unsaturated fatty acids in neuronal death. Evidence that metallothionein-rich astrocytes improve the viability of HD-patient-derived neurons in vitro.

Impaired DNA Repair Linked to Huntington's Disease Progression

A recent study suggests that impaired DNA repair mechanisms may contribute to Huntington's disease. The mutated huntingtin protein appears to hinder nerve cells from repairing damaged DNA, leading to cell death. Researchers found lower levels of poly ADP-ribose (PAR), a molecule essential for DNA repair, in the spinal fluid of Huntington's patients. This discovery opens up promising avenues for therapeutic intervention, as drugs targeting PAR production and degradation already exist. The study highlights the potential for early preventive therapies and suggests that PARP-targeting treatments, currently used in cancer, could be evaluated for Huntington's and other neurodegenerative diseases.

Researchers discover reason for disrupted DNA repair in Huntington's disease patients

McMaster researchers have discovered that the mutated huntingtin protein in Huntington's disease patients fails to repair DNA, impairing brain cell healing. This protein normally helps create Poly [ADP-ribose] (PAR) molecules, essential for DNA repair, but the mutation disrupts this process. Interestingly, lower PAR levels were found in Huntington's patients, contrary to other neurodegenerative diseases. This discovery links to cancer research, as PARP inhibitors used in cancer treatment might explain lower cancer rates in Huntington's gene carriers. Future studies will explore these findings further, potentially benefiting both Huntington's and cancer research.

Dysregulated Poly ADP-Ribose Signalling in Huntington Disease

Recent research has identified a deficiency in poly ADP-ribose (PAR) signalling in Huntington disease (HD) patients. This discovery contrasts with other neurodegenerative diseases where elevated PAR levels are common. The study found that the mutated huntingtin protein in HD patients fails to stimulate PAR production, unlike the wild-type protein. This insight opens new avenues for therapeutic interventions, as drugs targeting PAR production and degradation already exist. The research highlights that HD mutation carriers exhibit lower cerebrospinal fluid PAR levels even before symptoms manifest. This deficiency is also observed in patient-derived cells. The study further reveals that while both wild-type and mutant huntingtin proteins bind PAR similarly, only the wild-type protein enhances PARP1 activity. These findings suggest potential early preventive therapies for HD, offering hope for affected individuals and their families.