Hereditary hemorrhagic telangiectasia: from signaling insights to therapeutic advances
Hereditary hemorrhagic telangiectsia (HHT) is an inherited vascular disorder with highly variable expressivity, affecting up to 1 in 5,000 individuals. This disease is characterized by small arteriovenous malformations (AVMs) in mucocutaneous areas (telangiectases) and larger visceral AVMs in the lu...
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| Veröffentlicht in: | The Journal of clinical investigation 2024-02, Vol.134 (4) |
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| container_title | The Journal of clinical investigation |
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| creator | Al Tabosh, Tala Al Tarrass, Mohammad Tourvieilhe, Laura Guilhem, Alexandre Dupuis-Girod, Sophie Bailly, Sabine |
| description | Hereditary hemorrhagic telangiectsia (HHT) is an inherited vascular disorder with highly variable expressivity, affecting up to 1 in 5,000 individuals. This disease is characterized by small arteriovenous malformations (AVMs) in mucocutaneous areas (telangiectases) and larger visceral AVMs in the lungs, liver, and brain. HHT is caused by loss-of-function mutations in the BMP9-10/ENG/ALK1/SMAD4 signaling pathway. This Review presents up-to-date insights on this mutated signaling pathway and its crosstalk with proangiogenic pathways, in particular the VEGF pathway, that has allowed the repurposing of new drugs for HHT treatment. However, despite the substantial benefits of these new treatments in terms of alleviating symptom severity, this not-so-uncommon bleeding disorder still currently lacks any FDA- or European Medicines Agency-approved (EMA-approved) therapies. |
| doi_str_mv | 10.1172/JCI176379 |
| format | Article |
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This disease is characterized by small arteriovenous malformations (AVMs) in mucocutaneous areas (telangiectases) and larger visceral AVMs in the lungs, liver, and brain. HHT is caused by loss-of-function mutations in the BMP9-10/ENG/ALK1/SMAD4 signaling pathway. This Review presents up-to-date insights on this mutated signaling pathway and its crosstalk with proangiogenic pathways, in particular the VEGF pathway, that has allowed the repurposing of new drugs for HHT treatment. 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This disease is characterized by small arteriovenous malformations (AVMs) in mucocutaneous areas (telangiectases) and larger visceral AVMs in the lungs, liver, and brain. HHT is caused by loss-of-function mutations in the BMP9-10/ENG/ALK1/SMAD4 signaling pathway. This Review presents up-to-date insights on this mutated signaling pathway and its crosstalk with proangiogenic pathways, in particular the VEGF pathway, that has allowed the repurposing of new drugs for HHT treatment. However, despite the substantial benefits of these new treatments in terms of alleviating symptom severity, this not-so-uncommon bleeding disorder still currently lacks any FDA- or European Medicines Agency-approved (EMA-approved) therapies.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>38357927</pmid><doi>10.1172/JCI176379</doi><orcidid>https://orcid.org/0000-0002-8834-5526</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Arteriovenous Malformations - metabolism Causes of Development and progression Drug approval Drug therapy Genetic aspects Health aspects Humans Life Sciences Liver Physiological aspects Review Series Signal Transduction - genetics Telangiectasia, Hereditary Hemorrhagic Telangiectasia, Hereditary Hemorrhagic - drug therapy Telangiectasia, Hereditary Hemorrhagic - genetics Telangiectasis Vascular endothelial growth factor |
| title | Hereditary hemorrhagic telangiectasia: from signaling insights to therapeutic advances |
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