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Safety and immunogenicity of Fc‐EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects
In X‐linked hypohidrotic ectodermal dysplasia, the most frequent ectodermal dysplasia, an inherited deficiency of the signalling protein ectodysplasin A1 (EDA1) impairs the development of the skin and its appendages, various eccrine glands, and dentition. The severe hypohidrosis common to X‐linked h...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495278/ https://www.ncbi.nlm.nih.gov/pubmed/32250462 http://dx.doi.org/10.1111/bcp.14301 |
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author | Körber, Iris Klein, Ophir D. Morhart, Patrick Faschingbauer, Florian Grange, Dorothy K. Clarke, Angus Bodemer, Christine Maitz, Silvia Huttner, Kenneth Kirby, Neil Durand, Caroline Schneider, Holm |
author_facet | Körber, Iris Klein, Ophir D. Morhart, Patrick Faschingbauer, Florian Grange, Dorothy K. Clarke, Angus Bodemer, Christine Maitz, Silvia Huttner, Kenneth Kirby, Neil Durand, Caroline Schneider, Holm |
author_sort | Körber, Iris |
collection | PubMed |
description | In X‐linked hypohidrotic ectodermal dysplasia, the most frequent ectodermal dysplasia, an inherited deficiency of the signalling protein ectodysplasin A1 (EDA1) impairs the development of the skin and its appendages, various eccrine glands, and dentition. The severe hypohidrosis common to X‐linked hypohidrotic ectodermal dysplasia patients may lead to life‐threatening hyperthermia, especially during hot weather or febrile illness. Fc‐EDA, an EDA1 replacement protein known to prevent the disease in newborn animals, was tested in 2 clinical trials (human adults and neonates) and additionally administered under compassionate use to 3 infants in utero. The data support the safety of Fc‐EDA and efficacy if applied prenatally. Anti‐drug antibodies were detected after intravenous administration in adult males and nonpregnant females, but not in pregnant women when Fc‐EDA was delivered intra‐amniotically. Most importantly, there was no detectable immune response to the investigational drug in neonates treated by intravenous infusions and in infants who had received Fc‐EDA in utero. In conclusion, the safety profile of this drug encourages further development of prenatal EDA1 replacement therapy. |
format | Online Article Text |
id | pubmed-7495278 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74952782020-09-24 Safety and immunogenicity of Fc‐EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects Körber, Iris Klein, Ophir D. Morhart, Patrick Faschingbauer, Florian Grange, Dorothy K. Clarke, Angus Bodemer, Christine Maitz, Silvia Huttner, Kenneth Kirby, Neil Durand, Caroline Schneider, Holm Br J Clin Pharmacol Original Articles In X‐linked hypohidrotic ectodermal dysplasia, the most frequent ectodermal dysplasia, an inherited deficiency of the signalling protein ectodysplasin A1 (EDA1) impairs the development of the skin and its appendages, various eccrine glands, and dentition. The severe hypohidrosis common to X‐linked hypohidrotic ectodermal dysplasia patients may lead to life‐threatening hyperthermia, especially during hot weather or febrile illness. Fc‐EDA, an EDA1 replacement protein known to prevent the disease in newborn animals, was tested in 2 clinical trials (human adults and neonates) and additionally administered under compassionate use to 3 infants in utero. The data support the safety of Fc‐EDA and efficacy if applied prenatally. Anti‐drug antibodies were detected after intravenous administration in adult males and nonpregnant females, but not in pregnant women when Fc‐EDA was delivered intra‐amniotically. Most importantly, there was no detectable immune response to the investigational drug in neonates treated by intravenous infusions and in infants who had received Fc‐EDA in utero. In conclusion, the safety profile of this drug encourages further development of prenatal EDA1 replacement therapy. John Wiley and Sons Inc. 2020-04-24 2020-10 /pmc/articles/PMC7495278/ /pubmed/32250462 http://dx.doi.org/10.1111/bcp.14301 Text en © 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Körber, Iris Klein, Ophir D. Morhart, Patrick Faschingbauer, Florian Grange, Dorothy K. Clarke, Angus Bodemer, Christine Maitz, Silvia Huttner, Kenneth Kirby, Neil Durand, Caroline Schneider, Holm Safety and immunogenicity of Fc‐EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects |
title | Safety and immunogenicity of Fc‐EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects |
title_full | Safety and immunogenicity of Fc‐EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects |
title_fullStr | Safety and immunogenicity of Fc‐EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects |
title_full_unstemmed | Safety and immunogenicity of Fc‐EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects |
title_short | Safety and immunogenicity of Fc‐EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects |
title_sort | safety and immunogenicity of fc‐eda, a recombinant ectodysplasin a1 replacement protein, in human subjects |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495278/ https://www.ncbi.nlm.nih.gov/pubmed/32250462 http://dx.doi.org/10.1111/bcp.14301 |
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