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Advances in the management of erythropoietic protoporphyria – role of afamelanotide
Erythropoietic protoporphyria (EPP) and the phenotypically similar disease X-linked protoporphyria (XLPP) are inherited cutaneous porphyrias characterized clinically by acute non-blistering photosensitivity, intolerance to sunlight, and significantly reduced quality of life. They are due to marked o...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove Medical Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161401/ https://www.ncbi.nlm.nih.gov/pubmed/28003770 http://dx.doi.org/10.2147/TACG.S122030 |
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author | Lane, Ashley M McKay, Jerome T Bonkovsky, Herbert L |
author_facet | Lane, Ashley M McKay, Jerome T Bonkovsky, Herbert L |
author_sort | Lane, Ashley M |
collection | PubMed |
description | Erythropoietic protoporphyria (EPP) and the phenotypically similar disease X-linked protoporphyria (XLPP) are inherited cutaneous porphyrias characterized clinically by acute non-blistering photosensitivity, intolerance to sunlight, and significantly reduced quality of life. They are due to marked overproduction of protoporphyrin (PP) chiefly by erythroblasts and reticulocytes. In EPP, the underlying genetic defect is in the ferrochelatase gene, which encodes the final enzyme in the heme synthetic pathway. In XLPP, the genetic defect is a gain-of-function mutation, usually a four-base deletion, in the gene that encodes the enzyme 5-aminolevulinic acid synthase-2, the first and rate-controlling enzyme of heme synthesis in developing red blood cells. The excess PP causes acute and painful photosensitivity, being activated by light in the long ultraviolet to blue spectrum (380–420 nm, the Soret band). Although several treatments have been proposed, presently no very effective treatment exists for EPP or XLPP. Afamelanotide (Scenesse(®)) is a first-in-class synthetic analog of α-melanocyte stimulating hormone. Afamelanotide mimics the naturally occurring hormone to increase skin pigmentation by increasing melanin production in melanocytes, resulting in increased sunlight tolerance in those with EPP/XLPP. Afamelanotide is currently approved for use in the European Union and Switzerland, and it is under review in the United States by the Food and Drug Administration for use in patients with EPP/XLPP. This paper provides a review of the clinical characteristics and current therapies for EPP/XLPP. We discuss the pharmacology, clinical efficacy, safety, and tolerability of afamelanotide and summarize the results of several key Phase II and III clinical trials. These data indicate that afamelanotide is a promising therapy for those with these debilitating diseases. |
format | Online Article Text |
id | pubmed-5161401 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-51614012016-12-21 Advances in the management of erythropoietic protoporphyria – role of afamelanotide Lane, Ashley M McKay, Jerome T Bonkovsky, Herbert L Appl Clin Genet Review Erythropoietic protoporphyria (EPP) and the phenotypically similar disease X-linked protoporphyria (XLPP) are inherited cutaneous porphyrias characterized clinically by acute non-blistering photosensitivity, intolerance to sunlight, and significantly reduced quality of life. They are due to marked overproduction of protoporphyrin (PP) chiefly by erythroblasts and reticulocytes. In EPP, the underlying genetic defect is in the ferrochelatase gene, which encodes the final enzyme in the heme synthetic pathway. In XLPP, the genetic defect is a gain-of-function mutation, usually a four-base deletion, in the gene that encodes the enzyme 5-aminolevulinic acid synthase-2, the first and rate-controlling enzyme of heme synthesis in developing red blood cells. The excess PP causes acute and painful photosensitivity, being activated by light in the long ultraviolet to blue spectrum (380–420 nm, the Soret band). Although several treatments have been proposed, presently no very effective treatment exists for EPP or XLPP. Afamelanotide (Scenesse(®)) is a first-in-class synthetic analog of α-melanocyte stimulating hormone. Afamelanotide mimics the naturally occurring hormone to increase skin pigmentation by increasing melanin production in melanocytes, resulting in increased sunlight tolerance in those with EPP/XLPP. Afamelanotide is currently approved for use in the European Union and Switzerland, and it is under review in the United States by the Food and Drug Administration for use in patients with EPP/XLPP. This paper provides a review of the clinical characteristics and current therapies for EPP/XLPP. We discuss the pharmacology, clinical efficacy, safety, and tolerability of afamelanotide and summarize the results of several key Phase II and III clinical trials. These data indicate that afamelanotide is a promising therapy for those with these debilitating diseases. Dove Medical Press 2016-12-12 /pmc/articles/PMC5161401/ /pubmed/28003770 http://dx.doi.org/10.2147/TACG.S122030 Text en © 2016 Lane et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Review Lane, Ashley M McKay, Jerome T Bonkovsky, Herbert L Advances in the management of erythropoietic protoporphyria – role of afamelanotide |
title | Advances in the management of erythropoietic protoporphyria – role of afamelanotide |
title_full | Advances in the management of erythropoietic protoporphyria – role of afamelanotide |
title_fullStr | Advances in the management of erythropoietic protoporphyria – role of afamelanotide |
title_full_unstemmed | Advances in the management of erythropoietic protoporphyria – role of afamelanotide |
title_short | Advances in the management of erythropoietic protoporphyria – role of afamelanotide |
title_sort | advances in the management of erythropoietic protoporphyria – role of afamelanotide |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161401/ https://www.ncbi.nlm.nih.gov/pubmed/28003770 http://dx.doi.org/10.2147/TACG.S122030 |
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