Huntington’s disease (HD) is an autosomal dominant neurodegenerative condition characterised by motor, cognitive and neuropsychiatric symptoms, resulting from an expanded CAG trinucleotide repeat in the huntingtin (HTT) gene, leading to the accumulation of toxic mutant huntingtin (mHTT) protein. Despite the established geneticGenetics aetiology, the pathophysiology of HD is complex, and the lack of disease-modifying treatments accentuates the pressing need for effective therapeutic strategies. Recent advancements in HD research are increasingly directed towards gene-targeted therapies such as antisense oligonucleotides and small molecule splicing modifiers, aimed at reducing levels of toxic mHTT protein. Essential for the success of these emerging therapies is the need for biomarkersBiomarkers that reliably and robustly correlate with disease progression. Effects can be determined via biomarkers to assess target engagement and response to intervention at a cellular level (e.g. via biofluids) and at a macrostructural level (e.g. via imagingImaging). Herein, this chapter provides a comprehensive summary of the current landscape of fluidFluid and imaging biomarkers in HD and offers insights into the future trajectory of biomarker research in this era of HTT-lowering therapeutics.

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Fluid and Imaging Markers of Huntington’s Disease

  • Mena Farag,
  • Rachael I. Scahill,
  • Edward J. Wild,
  • Sarah J. Tabrizi

摘要

Huntington’s disease (HD) is an autosomal dominant neurodegenerative condition characterised by motor, cognitive and neuropsychiatric symptoms, resulting from an expanded CAG trinucleotide repeat in the huntingtin (HTT) gene, leading to the accumulation of toxic mutant huntingtin (mHTT) protein. Despite the established geneticGenetics aetiology, the pathophysiology of HD is complex, and the lack of disease-modifying treatments accentuates the pressing need for effective therapeutic strategies. Recent advancements in HD research are increasingly directed towards gene-targeted therapies such as antisense oligonucleotides and small molecule splicing modifiers, aimed at reducing levels of toxic mHTT protein. Essential for the success of these emerging therapies is the need for biomarkersBiomarkers that reliably and robustly correlate with disease progression. Effects can be determined via biomarkers to assess target engagement and response to intervention at a cellular level (e.g. via biofluids) and at a macrostructural level (e.g. via imagingImaging). Herein, this chapter provides a comprehensive summary of the current landscape of fluidFluid and imaging biomarkers in HD and offers insights into the future trajectory of biomarker research in this era of HTT-lowering therapeutics.