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Evaluation of mutant huntingtin and neurofilament proteins as potential markers in Huntington's disease.
Byrne, Lauren M; Rodrigues, Filipe B; Johnson, Eileanor B; Wijeratne, Peter A; De Vita, Enrico; Alexander, Daniel C; Palermo, Giuseppe; Czech, Christian; Schobel, Scott; Scahill, Rachael I; Heslegrave, Amanda; Zetterberg, Henrik; Wild, Edward J.
Afiliação
  • Byrne LM; Huntington's Disease Centre, University College London (UCL) Institute of Neurology, London WC1N 3BG, UK. lauren.byrne.14@ucl.ac.uk e.wild@ucl.ac.uk.
  • Rodrigues FB; Huntington's Disease Centre, University College London (UCL) Institute of Neurology, London WC1N 3BG, UK.
  • Johnson EB; Huntington's Disease Centre, University College London (UCL) Institute of Neurology, London WC1N 3BG, UK.
  • Wijeratne PA; Centre for Medical Image Computing, Department of Computer Science, UCL, London WC1E 6EA, UK.
  • De Vita E; Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK.
  • Alexander DC; Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Sciences, King's College London, London SE1 7EH, UK.
  • Palermo G; Centre for Medical Image Computing, Department of Computer Science, UCL, London WC1E 6EA, UK.
  • Czech C; Clinical Imaging Research Centre, National University of Singapore, Singapore 117599, Singapore.
  • Schobel S; Neuroscience, Ophthalmology, and Rare Diseases, Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffman-La Roche Ltd., 4070 Basel, Switzerland.
  • Scahill RI; Neuroscience, Ophthalmology, and Rare Diseases, Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffman-La Roche Ltd., 4070 Basel, Switzerland.
  • Heslegrave A; Neuroscience, Ophthalmology, and Rare Diseases, Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffman-La Roche Ltd., 4070 Basel, Switzerland.
  • Zetterberg H; Huntington's Disease Centre, University College London (UCL) Institute of Neurology, London WC1N 3BG, UK.
  • Wild EJ; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Sci Transl Med ; 10(458)2018 09 12.
Article em En | MEDLINE | ID: mdl-30209243
ABSTRACT
Huntington's disease (HD) is a genetic progressive neurodegenerative disorder, caused by a mutation in the HTT gene, for which there is currently no cure. The identification of sensitive indicators of disease progression and therapeutic outcome could help the development of effective strategies for treating HD. We assessed mutant huntingtin (mHTT) and neurofilament light (NfL) protein concentrations in cerebrospinal fluid (CSF) and blood in parallel with clinical evaluation and magnetic resonance imaging in premanifest and manifest HD mutation carriers. Among HD mutation carriers, NfL concentrations in plasma and CSF correlated with all nonbiofluid measures more closely than did CSF mHTT concentration. Longitudinal analysis over 4 to 8 weeks showed that CSF mHTT, CSF NfL, and plasma NfL concentrations were highly stable within individuals. In our cohort, concentration of CSF mHTT accurately distinguished between controls and HD mutation carriers, whereas NfL concentration, in both CSF and plasma, was able to segregate premanifest from manifest HD. In silico modeling indicated that mHTT and NfL concentrations in biofluids might be among the earliest detectable alterations in HD, and sample size prediction suggested that low participant numbers would be needed to incorporate these measures into clinical trials. These findings provide evidence that biofluid concentrations of mHTT and NfL have potential for early and sensitive detection of alterations in HD and could be integrated into both clinical trials and the clinic.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Biomarcadores / Proteínas de Neurofilamentos / Doença de Huntington / Proteína Huntingtina Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Biomarcadores / Proteínas de Neurofilamentos / Doença de Huntington / Proteína Huntingtina Idioma: En Ano de publicação: 2018 Tipo de documento: Article