High throughput testing of drug library substances and monoclonal antibodies for capacity to reduce formation of cystatin C dimers to identify candidates for treatment of hereditary cystatin C amyloid angiopathy.
Östner, Gustav LU ; Lindström, Veronica LU
; Postnikov, Alexander B
; Solovyeva, Tatiana I
; Emilsson, Ossur I
and Grubb, Anders
LU
(2011)
In Scandinavian Journal of Clinical and Laboratory Investigation
71(8).
p.676-682
- Abstract
- Objective. To establish a high-throughput system for testing the ability of drugs or monoclonal antibodies to reduce the in vitro formation of cystatin C dimers to identify substances potentially useful for treatment of patients with hereditary cystatin C amyloid angiopathy (HCCAA). Methods. Various combinations of incubation temperature, time period, guanidinium chloride concentration and concentration of cystatin C monomers were tested in low-volume formats to induce dimer formation of recombinant cystatin C. The extent of dimerization was analysed by gel filtration chromatography and agarose gel electrophoresis. Results. A high-throughput system based upon agarose gel electrophoresis was developed and used to test 1040 drugs in a... (More)
- Objective. To establish a high-throughput system for testing the ability of drugs or monoclonal antibodies to reduce the in vitro formation of cystatin C dimers to identify substances potentially useful for treatment of patients with hereditary cystatin C amyloid angiopathy (HCCAA). Methods. Various combinations of incubation temperature, time period, guanidinium chloride concentration and concentration of cystatin C monomers were tested in low-volume formats to induce dimer formation of recombinant cystatin C. The extent of dimerization was analysed by gel filtration chromatography and agarose gel electrophoresis. Results. A high-throughput system based upon agarose gel electrophoresis was developed and used to test 1040 drugs in a clinical drug library for their capacity to reduce cystatin C dimer formation in vitro. Seventeen substances reducing dimer formation by more than 30% were identified. A similar system for testing the capacity of monoclonal antibodies against cystatin C to reduce the in vitro formation of cystatin C dimers was also developed and used to test a panel of 12 monoclonal antibodies. Seven antibodies reducing dimer formation by more than 30% were identified and the two most potent, Cyst28 and HCC3, reduced dimerization by 75 and 60%, respectively. Conclusion. We constructed a simple high-throughput system for testing the capacity of drugs and monoclonal antibodies to reduce the in vitro formation of cystatin C dimers and several candidates for treatment of HCCAA could be identified. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2200320
- author
- Östner, Gustav
LU
; Lindström, Veronica
LU
; Postnikov, Alexander B
; Solovyeva, Tatiana I
; Emilsson, Ossur I
and Grubb, Anders
LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scandinavian Journal of Clinical and Laboratory Investigation
- volume
- 71
- issue
- 8
- pages
- 676 - 682
- publisher
- Informa Healthcare
- external identifiers
-
- wos:000296980600010
- pmid:22017167
- scopus:81255143205
- pmid:22017167
- ISSN
- 1502-7686
- DOI
- 10.3109/00365513.2011.621026
- language
- English
- LU publication?
- yes
- id
- 2db7ad00-f988-445a-b520-dd3283a0e2b1 (old id 2200320)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22017167?dopt=Abstract
- date added to LUP
- 2016-04-01 13:46:47
- date last changed
- 2023-01-04 00:51:14
@article{2db7ad00-f988-445a-b520-dd3283a0e2b1,
abstract = {{Objective. To establish a high-throughput system for testing the ability of drugs or monoclonal antibodies to reduce the in vitro formation of cystatin C dimers to identify substances potentially useful for treatment of patients with hereditary cystatin C amyloid angiopathy (HCCAA). Methods. Various combinations of incubation temperature, time period, guanidinium chloride concentration and concentration of cystatin C monomers were tested in low-volume formats to induce dimer formation of recombinant cystatin C. The extent of dimerization was analysed by gel filtration chromatography and agarose gel electrophoresis. Results. A high-throughput system based upon agarose gel electrophoresis was developed and used to test 1040 drugs in a clinical drug library for their capacity to reduce cystatin C dimer formation in vitro. Seventeen substances reducing dimer formation by more than 30% were identified. A similar system for testing the capacity of monoclonal antibodies against cystatin C to reduce the in vitro formation of cystatin C dimers was also developed and used to test a panel of 12 monoclonal antibodies. Seven antibodies reducing dimer formation by more than 30% were identified and the two most potent, Cyst28 and HCC3, reduced dimerization by 75 and 60%, respectively. Conclusion. We constructed a simple high-throughput system for testing the capacity of drugs and monoclonal antibodies to reduce the in vitro formation of cystatin C dimers and several candidates for treatment of HCCAA could be identified.}},
author = {{Östner, Gustav and Lindström, Veronica and Postnikov, Alexander B and Solovyeva, Tatiana I and Emilsson, Ossur I and Grubb, Anders}},
issn = {{1502-7686}},
language = {{eng}},
number = {{8}},
pages = {{676--682}},
publisher = {{Informa Healthcare}},
series = {{Scandinavian Journal of Clinical and Laboratory Investigation}},
title = {{High throughput testing of drug library substances and monoclonal antibodies for capacity to reduce formation of cystatin C dimers to identify candidates for treatment of hereditary cystatin C amyloid angiopathy.}},
url = {{https://lup.lub.lu.se/search/files/3583815/2294148.pdf}},
doi = {{10.3109/00365513.2011.621026}},
volume = {{71}},
year = {{2011}},
}