Future treatments for hereditary hemorrhagic telangiectasia
Abstract Hereditary Hemorrhagic Telangiectasia (HHT), also known as Rendu-Osler syndrome, is a genetic vascular disorder affecting 1 in 5000–8000 individuals worldwide. This rare disease is characterized by various vascular defects including epistaxis, blood vessel dilations (telangiectasia) and art...
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| Format: | Article |
| Language: | English |
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BMC
2020-01-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-019-1281-4 |
| _version_ | 1818417204909047808 |
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| author | Florian Robert Agnès Desroches-Castan Sabine Bailly Sophie Dupuis-Girod Jean-Jacques Feige |
| author_facet | Florian Robert Agnès Desroches-Castan Sabine Bailly Sophie Dupuis-Girod Jean-Jacques Feige |
| author_sort | Florian Robert |
| collection | DOAJ |
| description | Abstract Hereditary Hemorrhagic Telangiectasia (HHT), also known as Rendu-Osler syndrome, is a genetic vascular disorder affecting 1 in 5000–8000 individuals worldwide. This rare disease is characterized by various vascular defects including epistaxis, blood vessel dilations (telangiectasia) and arteriovenous malformations (AVM) in several organs. About 90% of the cases are associated with heterozygous mutations of ACVRL1 or ENG genes, that respectively encode a bone morphogenetic protein receptor (activin receptor-like kinase 1, ALK1) and a co-receptor named endoglin. Less frequent mutations found in the remaining 10% of patients also affect the gene SMAD4 which is part of the transcriptional complex directly activated by this pathway. Presently, the therapeutic treatments for HHT are intended to reduce the symptoms of the disease. However, recent progress has been made using drugs that target VEGF (vascular endothelial growth factor) and the angiogenic pathway with the use of bevacizumab (anti-VEGF antibody). Furthermore, several exciting high-throughput screenings and preclinical studies have identified new molecular targets directly related to the signaling pathways affected in the disease. These include FKBP12, PI3-kinase and angiopoietin-2. This review aims at reporting these recent developments that should soon allow a better care of HHT patients. |
| first_indexed | 2024-12-14T12:03:04Z |
| format | Article |
| id | doaj.art-58e4a05c1ce9485e874117ded0f49af4 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-14T12:03:04Z |
| publishDate | 2020-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-58e4a05c1ce9485e874117ded0f49af42022-12-21T23:01:56ZengBMCOrphanet Journal of Rare Diseases1750-11722020-01-0115111010.1186/s13023-019-1281-4Future treatments for hereditary hemorrhagic telangiectasiaFlorian Robert0Agnès Desroches-Castan1Sabine Bailly2Sophie Dupuis-Girod3Jean-Jacques Feige4Univ. Grenoble Alpes, Inserm, CEA, Laboratory Biology of Cancer and InfectionUniv. Grenoble Alpes, Inserm, CEA, Laboratory Biology of Cancer and InfectionUniv. Grenoble Alpes, Inserm, CEA, Laboratory Biology of Cancer and InfectionUniv. Grenoble Alpes, Inserm, CEA, Laboratory Biology of Cancer and InfectionUniv. Grenoble Alpes, Inserm, CEA, Laboratory Biology of Cancer and InfectionAbstract Hereditary Hemorrhagic Telangiectasia (HHT), also known as Rendu-Osler syndrome, is a genetic vascular disorder affecting 1 in 5000–8000 individuals worldwide. This rare disease is characterized by various vascular defects including epistaxis, blood vessel dilations (telangiectasia) and arteriovenous malformations (AVM) in several organs. About 90% of the cases are associated with heterozygous mutations of ACVRL1 or ENG genes, that respectively encode a bone morphogenetic protein receptor (activin receptor-like kinase 1, ALK1) and a co-receptor named endoglin. Less frequent mutations found in the remaining 10% of patients also affect the gene SMAD4 which is part of the transcriptional complex directly activated by this pathway. Presently, the therapeutic treatments for HHT are intended to reduce the symptoms of the disease. However, recent progress has been made using drugs that target VEGF (vascular endothelial growth factor) and the angiogenic pathway with the use of bevacizumab (anti-VEGF antibody). Furthermore, several exciting high-throughput screenings and preclinical studies have identified new molecular targets directly related to the signaling pathways affected in the disease. These include FKBP12, PI3-kinase and angiopoietin-2. This review aims at reporting these recent developments that should soon allow a better care of HHT patients.https://doi.org/10.1186/s13023-019-1281-4Hereditary hemorrhagic telangiectasiaVascular malformationsBone morphogenetic protein signalingDrug repositioningBevacizumabTacrolimus |
| spellingShingle | Florian Robert Agnès Desroches-Castan Sabine Bailly Sophie Dupuis-Girod Jean-Jacques Feige Future treatments for hereditary hemorrhagic telangiectasia Orphanet Journal of Rare Diseases Hereditary hemorrhagic telangiectasia Vascular malformations Bone morphogenetic protein signaling Drug repositioning Bevacizumab Tacrolimus |
| title | Future treatments for hereditary hemorrhagic telangiectasia |
| title_full | Future treatments for hereditary hemorrhagic telangiectasia |
| title_fullStr | Future treatments for hereditary hemorrhagic telangiectasia |
| title_full_unstemmed | Future treatments for hereditary hemorrhagic telangiectasia |
| title_short | Future treatments for hereditary hemorrhagic telangiectasia |
| title_sort | future treatments for hereditary hemorrhagic telangiectasia |
| topic | Hereditary hemorrhagic telangiectasia Vascular malformations Bone morphogenetic protein signaling Drug repositioning Bevacizumab Tacrolimus |
| url | https://doi.org/10.1186/s13023-019-1281-4 |
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