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Future treatments for hereditary hemorrhagic telangiectasia
- Source :
- Orphanet Journal of Rare Diseases, Vol 15, Iss 1, Pp 1-10 (2020), Orphanet Journal of Rare Diseases, Orphanet Journal of Rare Diseases, 2020, 15 (1), pp.4. ⟨10.1186/s13023-019-1281-4⟩
- Publication Year :
- 2020
- Publisher :
- BMC, 2020.
-
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 ofACVRL1orENGgenes, 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 geneSMAD4which 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.
- Subjects :
- 0301 basic medicine
Bone morphogenetic protein signaling
[SDV]Life Sciences [q-bio]
Vascular malformations
lcsh:Medicine
Disease
Review
ALK1
030204 cardiovascular system & hematology
Tacrolimus
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
High throughput screening
Medicine
Humans
Pharmacology (medical)
Bone morphogenetic protein receptor
Telangiectasia
Genetics (clinical)
Smad4 Protein
business.industry
Drug repositioning
lcsh:R
ACVRL1
General Medicine
Endoglin
High-Throughput Screening Assays
Vascular endothelial growth factor
Bevacizumab
030104 developmental biology
chemistry
Hereditary hemorrhagic telangiectasia
Vascular Disorder
Cancer research
Telangiectasia, Hereditary Hemorrhagic
medicine.symptom
business
Rare disease
Subjects
Details
- Language :
- English
- ISSN :
- 17501172
- Volume :
- 15
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Orphanet Journal of Rare Diseases
- Accession number :
- edsair.doi.dedup.....0854ac2f923994ea782e04613909b0fc