Matches in SemOpenAlex for { <https://semopenalex.org/work/W4362520610> ?p ?o ?g. }
- W4362520610 abstract "Huntington's disease (HD) is caused by a cytosine adenine guanine-repeat expansion in the huntingtin gene. This results in the production of toxic mutant huntingtin protein (mHTT), which has an elongated polyglutamine (polyQ) stretch near the protein's N-terminal end. The pharmacological lowering of mHTT expression in the brain targets the underlying driver of HD and is one of the principal therapeutic strategies being pursued to slow or stop disease progression. This report describes the characterisation and validation of an assay designed to quantify mHTT in the cerebrospinal fluid of individuals with HD, for use in registrational clinical trials. The assay was optimised, and its performance was characterised with recombinant huntingtin protein (HTT) varying in overall and polyQ-repeat length. The assay was successfully validated by two independent laboratories in regulated bioanalytical environments and showed a steep signal increase as the polyQ stretch of recombinant HTTs pivoted from wild-type to mutant protein forms. Linear mixed effects modelling confirmed highly parallel concentration-response curves for HTTs, with only a minor impact of individual slopes of the concentration-response for different HTTs (typically < 5% of the overall slope). This implies an equivalent quantitative signal behaviour for HTTs with differing polyQ-repeat lengths. The reported method may be a reliable biomarker tool with relevance across the spectrum of HD mutations, which can facilitate the clinical development of HTT-lowering therapies in HD." @default.
- W4362520610 created "2023-04-06" @default.
- W4362520610 creator A5005910368 @default.
- W4362520610 creator A5006993893 @default.
- W4362520610 creator A5010717623 @default.
- W4362520610 creator A5025159976 @default.
- W4362520610 creator A5028829972 @default.
- W4362520610 creator A5030144835 @default.
- W4362520610 creator A5035924485 @default.
- W4362520610 creator A5042904716 @default.
- W4362520610 creator A5088079816 @default.
- W4362520610 date "2023-04-01" @default.
- W4362520610 modified "2023-10-18" @default.
- W4362520610 title "Quantifying mutant huntingtin protein in human cerebrospinal fluid to support the development of huntingtin-lowering therapies" @default.
- W4362520610 cites W1966151464 @default.
- W4362520610 cites W1969496807 @default.
- W4362520610 cites W1975583867 @default.
- W4362520610 cites W1975932182 @default.
- W4362520610 cites W2020117714 @default.
- W4362520610 cites W2063702351 @default.
- W4362520610 cites W2076843567 @default.
- W4362520610 cites W2127538769 @default.
- W4362520610 cites W2153421357 @default.
- W4362520610 cites W2166950919 @default.
- W4362520610 cites W2167093496 @default.
- W4362520610 cites W2271390580 @default.
- W4362520610 cites W2291779372 @default.
- W4362520610 cites W2415002142 @default.
- W4362520610 cites W2738381203 @default.
- W4362520610 cites W2767946212 @default.
- W4362520610 cites W2891872689 @default.
- W4362520610 cites W2919539529 @default.
- W4362520610 cites W2994977411 @default.
- W4362520610 cites W3110716355 @default.
- W4362520610 cites W3161712179 @default.
- W4362520610 cites W4210584483 @default.
- W4362520610 cites W4282972828 @default.
- W4362520610 cites W4282979939 @default.
- W4362520610 cites W4293733558 @default.
- W4362520610 cites W4302568911 @default.
- W4362520610 doi "https://doi.org/10.1038/s41598-023-32630-4" @default.
- W4362520610 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37005488" @default.
- W4362520610 hasPublicationYear "2023" @default.
- W4362520610 type Work @default.
- W4362520610 citedByCount "0" @default.
- W4362520610 crossrefType "journal-article" @default.
- W4362520610 hasAuthorship W4362520610A5005910368 @default.
- W4362520610 hasAuthorship W4362520610A5006993893 @default.
- W4362520610 hasAuthorship W4362520610A5010717623 @default.
- W4362520610 hasAuthorship W4362520610A5025159976 @default.
- W4362520610 hasAuthorship W4362520610A5028829972 @default.
- W4362520610 hasAuthorship W4362520610A5030144835 @default.
- W4362520610 hasAuthorship W4362520610A5035924485 @default.
- W4362520610 hasAuthorship W4362520610A5042904716 @default.
- W4362520610 hasAuthorship W4362520610A5088079816 @default.
- W4362520610 hasBestOaLocation W43625206101 @default.
- W4362520610 hasConcept C104317684 @default.
- W4362520610 hasConcept C126322002 @default.
- W4362520610 hasConcept C143065580 @default.
- W4362520610 hasConcept C153911025 @default.
- W4362520610 hasConcept C185592680 @default.
- W4362520610 hasConcept C2779134260 @default.
- W4362520610 hasConcept C2779926675 @default.
- W4362520610 hasConcept C2780647506 @default.
- W4362520610 hasConcept C2781197716 @default.
- W4362520610 hasConcept C2781427258 @default.
- W4362520610 hasConcept C2910011555 @default.
- W4362520610 hasConcept C40767141 @default.
- W4362520610 hasConcept C54355233 @default.
- W4362520610 hasConcept C71924100 @default.
- W4362520610 hasConcept C86803240 @default.
- W4362520610 hasConceptScore W4362520610C104317684 @default.
- W4362520610 hasConceptScore W4362520610C126322002 @default.
- W4362520610 hasConceptScore W4362520610C143065580 @default.
- W4362520610 hasConceptScore W4362520610C153911025 @default.
- W4362520610 hasConceptScore W4362520610C185592680 @default.
- W4362520610 hasConceptScore W4362520610C2779134260 @default.
- W4362520610 hasConceptScore W4362520610C2779926675 @default.
- W4362520610 hasConceptScore W4362520610C2780647506 @default.
- W4362520610 hasConceptScore W4362520610C2781197716 @default.
- W4362520610 hasConceptScore W4362520610C2781427258 @default.
- W4362520610 hasConceptScore W4362520610C2910011555 @default.
- W4362520610 hasConceptScore W4362520610C40767141 @default.
- W4362520610 hasConceptScore W4362520610C54355233 @default.
- W4362520610 hasConceptScore W4362520610C71924100 @default.
- W4362520610 hasConceptScore W4362520610C86803240 @default.
- W4362520610 hasFunder F4320307779 @default.
- W4362520610 hasIssue "1" @default.
- W4362520610 hasLocation W43625206101 @default.
- W4362520610 hasLocation W43625206102 @default.
- W4362520610 hasOpenAccess W4362520610 @default.
- W4362520610 hasPrimaryLocation W43625206101 @default.
- W4362520610 hasRelatedWork W1542702722 @default.
- W4362520610 hasRelatedWork W1594072754 @default.
- W4362520610 hasRelatedWork W1999783230 @default.
- W4362520610 hasRelatedWork W2029658443 @default.
- W4362520610 hasRelatedWork W2132357350 @default.
- W4362520610 hasRelatedWork W2390995953 @default.
- W4362520610 hasRelatedWork W2789662870 @default.
- W4362520610 hasRelatedWork W2952452438 @default.