Search: onr:"swepub:oai:gup.ub.gu.se/281605" >
Prion protein quant...
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
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
- By the author/editor
-
Vallabh, S. M.
-
Nobuhara, C. K.
-
Llorens, F.
-
Zerr, I.
-
Parchi, P.
-
Capellari, S.
-
show more...
-
Kuhn, E.
-
Klickstein, J.
-
Safar, J. G.
-
Nery, F. C.
-
Swoboda, K. J.
-
Geschwind, M. D.
-
Zetterberg, Henr ...
-
Arnold, S. E.
-
Minikel, E. V.
-
Schreiber, S. L.
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Neurosciences
- Articles in the publication
-
Proceedings of t ...
-
Proceedings of t ...
- By the university
-
University of Gothenburg