SwePub
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:gup.ub.gu.se/281605"
 

Search: onr:"swepub:oai:gup.ub.gu.se/281605" > Prion protein quant...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist
  • Vallabh, S. M. (author)

Prion protein quantification in human cerebrospinal fluid as a tool for prion disease drug development

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-04
  • Proceedings of the National Academy of Sciences,2019

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/281605
  • https://gup.ub.gu.se/publication/281605URI
  • https://doi.org/10.1073/pnas.1901947116DOI

Supplementary language notes

  • Language:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Reduction of native prion protein (PrP) levels in the brain is an attractive strategy for the treatment or prevention of human prion disease. Clinical development of any PrP-reducing therapeutic will require an appropriate pharmacodynamic biomarker: a practical and robust method for quantifying PrP, and reliably demonstrating its reduction in the central nervous system (CNS) of a living patient. Here we evaluate the potential of ELISA-based quantification of human PrP in human cerebrospinal fluid (CSF) to serve as a biomarker for PrP-reducing therapeutics. We show that CSF PrP is highly sensitive to plastic adsorption during handling and storage, but its loss can be minimized by the addition of detergent. We find that blood contamination does not affect CSF PrP levels, and that CSF PrP and hemoglobin are uncorrelated, together suggesting that CSF PrP is CNS derived, supporting its relevance for monitoring the tissue of interest and in keeping with high PrP abundance in brain relative to blood. In a cohort with controlled sample handling, CSF PrP exhibits good within-subject test–retest reliability (mean coefficient of variation, 13% in samples collected 8–11 wk apart), a sufficiently stable baseline to allow therapeutically meaningful reductions in brain PrP to be readily detected in CSF. Together, these findings supply a method for monitoring the effect of a PrP-reducing drug in the CNS, and will facilitate development of prion disease therapeutics with this mechanism of action. © 2019 National Academy of Sciences. All rights reserved.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Nobuhara, C. K. (author)
  • Llorens, F. (author)
  • Zerr, I. (author)
  • Parchi, P. (author)
  • Capellari, S. (author)
  • Kuhn, E. (author)
  • Klickstein, J. (author)
  • Safar, J. G. (author)
  • Nery, F. C. (author)
  • Swoboda, K. J. (author)
  • Geschwind, M. D. (author)
  • Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe (author)
  • Arnold, S. E. (author)
  • Minikel, E. V. (author)
  • Schreiber, S. L. (author)
  • Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

Related titles

  • In:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences116:16, s. 7793-77980027-8424
  • In:Proceedings of the National Academy of Sciences: Proceedings of the National Academy of Sciences116:16, s. 7793-77981091-6490

Internet link

Find in a library

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view