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“Endothelial Antibody Factory” at the Blood Brain Barrier: Novel Approach to Therapy of Neurodegenerative Diseases

The failures of anti-β-amyloid immunotherapies suggested that the very low fraction of injected antibodies reaching the brain parenchyma due to the filtering effect of the BBB may be a reason for the lack of therapeutic effect. However, there is no treatment, as yet, for the amyotrophic lateral scle...

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Autores principales: Thinard, Reynald, Farkas, Attila E., Halasa, Marta, Chevalier, Melanie, Brodaczewska, Klaudia, Majewska, Aleksandra, Zdanowski, Robert, Paprocka, Maria, Rossowska, Joanna, Duc, Lam Tri, Greferath, Ruth, Krizbai, Istvan, Van Leuven, Fred, Kieda, Claudine, Nicolau, Claude
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320725/
https://www.ncbi.nlm.nih.gov/pubmed/35890313
http://dx.doi.org/10.3390/pharmaceutics14071418
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author Thinard, Reynald
Farkas, Attila E.
Halasa, Marta
Chevalier, Melanie
Brodaczewska, Klaudia
Majewska, Aleksandra
Zdanowski, Robert
Paprocka, Maria
Rossowska, Joanna
Duc, Lam Tri
Greferath, Ruth
Krizbai, Istvan
Van Leuven, Fred
Kieda, Claudine
Nicolau, Claude
author_facet Thinard, Reynald
Farkas, Attila E.
Halasa, Marta
Chevalier, Melanie
Brodaczewska, Klaudia
Majewska, Aleksandra
Zdanowski, Robert
Paprocka, Maria
Rossowska, Joanna
Duc, Lam Tri
Greferath, Ruth
Krizbai, Istvan
Van Leuven, Fred
Kieda, Claudine
Nicolau, Claude
author_sort Thinard, Reynald
collection PubMed
description The failures of anti-β-amyloid immunotherapies suggested that the very low fraction of injected antibodies reaching the brain parenchyma due to the filtering effect of the BBB may be a reason for the lack of therapeutic effect. However, there is no treatment, as yet, for the amyotrophic lateral sclerosis (ALS) despite substantial evidence existing of the involvement of TDP-43 protein in the evolution of ALS. To circumvent this filtering effect, we have developed a novel approach to facilitate the penetration of antibody fragments (Fabs) into the brain parenchyma. Leveraging the homing properties of endothelial progenitor cells (EPCs), we transfected, ex vivo, such cells with vectors encoding anti-β-amyloid and anti-TDP43 Fabs turning them into an “antibody fragment factory”. When injected these cells integrate into the BBB, where they secrete anti-TDP43 Fabs. The results showed the formation of tight junctions between the injected engineered EPCs and the unlabeled resident endothelial cells. When the EPCs were further modified to express the anti-TDP43 Fab, we could observe integration of these cells into the vasculature and the secretion of Fabs. Results confirm that production and secretion of Fabs at the BBB level leads to their migration to the brain parenchyma where they might exert a therapeutic effect.
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spelling pubmed-93207252022-07-27 “Endothelial Antibody Factory” at the Blood Brain Barrier: Novel Approach to Therapy of Neurodegenerative Diseases Thinard, Reynald Farkas, Attila E. Halasa, Marta Chevalier, Melanie Brodaczewska, Klaudia Majewska, Aleksandra Zdanowski, Robert Paprocka, Maria Rossowska, Joanna Duc, Lam Tri Greferath, Ruth Krizbai, Istvan Van Leuven, Fred Kieda, Claudine Nicolau, Claude Pharmaceutics Article The failures of anti-β-amyloid immunotherapies suggested that the very low fraction of injected antibodies reaching the brain parenchyma due to the filtering effect of the BBB may be a reason for the lack of therapeutic effect. However, there is no treatment, as yet, for the amyotrophic lateral sclerosis (ALS) despite substantial evidence existing of the involvement of TDP-43 protein in the evolution of ALS. To circumvent this filtering effect, we have developed a novel approach to facilitate the penetration of antibody fragments (Fabs) into the brain parenchyma. Leveraging the homing properties of endothelial progenitor cells (EPCs), we transfected, ex vivo, such cells with vectors encoding anti-β-amyloid and anti-TDP43 Fabs turning them into an “antibody fragment factory”. When injected these cells integrate into the BBB, where they secrete anti-TDP43 Fabs. The results showed the formation of tight junctions between the injected engineered EPCs and the unlabeled resident endothelial cells. When the EPCs were further modified to express the anti-TDP43 Fab, we could observe integration of these cells into the vasculature and the secretion of Fabs. Results confirm that production and secretion of Fabs at the BBB level leads to their migration to the brain parenchyma where they might exert a therapeutic effect. MDPI 2022-07-06 /pmc/articles/PMC9320725/ /pubmed/35890313 http://dx.doi.org/10.3390/pharmaceutics14071418 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Thinard, Reynald
Farkas, Attila E.
Halasa, Marta
Chevalier, Melanie
Brodaczewska, Klaudia
Majewska, Aleksandra
Zdanowski, Robert
Paprocka, Maria
Rossowska, Joanna
Duc, Lam Tri
Greferath, Ruth
Krizbai, Istvan
Van Leuven, Fred
Kieda, Claudine
Nicolau, Claude
“Endothelial Antibody Factory” at the Blood Brain Barrier: Novel Approach to Therapy of Neurodegenerative Diseases
title “Endothelial Antibody Factory” at the Blood Brain Barrier: Novel Approach to Therapy of Neurodegenerative Diseases
title_full “Endothelial Antibody Factory” at the Blood Brain Barrier: Novel Approach to Therapy of Neurodegenerative Diseases
title_fullStr “Endothelial Antibody Factory” at the Blood Brain Barrier: Novel Approach to Therapy of Neurodegenerative Diseases
title_full_unstemmed “Endothelial Antibody Factory” at the Blood Brain Barrier: Novel Approach to Therapy of Neurodegenerative Diseases
title_short “Endothelial Antibody Factory” at the Blood Brain Barrier: Novel Approach to Therapy of Neurodegenerative Diseases
title_sort “endothelial antibody factory” at the blood brain barrier: novel approach to therapy of neurodegenerative diseases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320725/
https://www.ncbi.nlm.nih.gov/pubmed/35890313
http://dx.doi.org/10.3390/pharmaceutics14071418
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