|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
GermlineCausalMutation
|
disease |
ORPHANET |
In an effort to search for clinically applicable drugs for FOP, we screened 1,040 FDA-approved drugs for suppression of the Id1 promoter activated by the mutant ACVR1/ALK2 in C2C12 cells.
|
23011467 |
2013 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
CausalMutation
|
disease |
CLINVAR |
|
|
|
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
Our results therefore provide a potential therapeutic approach for the treatment of FOP disease by reducing the excessive ALK2 activity in FOP patients.
|
23861958 |
2013 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
Protein modeling predicts that substitution with histidine, and only histidine, creates a pH-sensitive switch within the activation domain of the receptor that leads to ligand-independent activation of ACVR1 in fibrodysplasia ossificans progressiva.
|
17572636 |
2007 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
Here, we describe a method to reduce ACVR1 expression in FOP patient cells by exon skipping in ACVR1 mRNAs using phosphorodiamidate morpholino oligomers (PMOs).
|
30171563 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
Protein modeling predicts destabilization of the GS domain, consistent with constitutive activation of ACVR1 as the underlying cause of the ectopic chondrogenesis, osteogenesis and joint fusions seen in FOP.
|
16642017 |
2006 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
We have determined that the formation of heterotopic bone in FOP requires activation of mutant ACVR1 by Activin A, in part by showing that prophylactic inhibition of Activin A blocks HO in a mouse model of FOP.
|
28782882 |
2017 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
Although Activin-A increased activation of the pSMAD3 pathway in both control and FOP PLF, it increased ACVR1, FK binding protein 12 (FKBP12), an inhibitor of DNA binding 1 protein (ID-1) expression only in FOP PLF.
|
30417373 |
2019 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
The causative gene of FOP is activin A receptor type 1 (ACVR1), a bone morphogenetic protein-signalling component, which normally acts to inhibit osteoblastogenesis.
|
31290775 |
2019 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
|
|
|
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
Surprisingly, the designated ATM inhibitor CP466722 was found to bind strongly to ALK2, identifying a new chemotype for drug discovery to treat fibrodysplasia ossificans progressiva.
|
30901187 |
2019 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
Compared with control cells FOP-ALK2-expressing cells induced increased bone formation.
|
19929436 |
2010 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
Due to lack of understanding of the etiology and progression of human FOP, and the fact that surgical interventions often exacerbate FOP disease progression, alternative therapeutic methods are needed, including modeling in animals, to study and improve understanding of human FOP.
|
29139166 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
The identification of ACVR1 as the causative gene for FOP now allows the genetic screening of FOP patients to identify the frequency of the identified recurrent ACVR1 mutation and to investigate genetic variability that may be associated with this severely debilitating disease.
|
18830232 |
2009 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
This study suggests miR-148a is an important mediator of ACVR1, thus offering a new potential target for the development of therapeutic agents against FOP.
|
22408438 |
2012 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
We studied 72 patients with FOP in China and analyzed their phenotypes and genotypes comprising the world's largest ethnically homogeneous population of FOP patients.
|
24051199 |
2013 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
These results uncovered the crucial role of the Activin-A/FOP-ACVR1/ENPP2/mTOR axis in FOP pathogenesis.
|
28758906 |
2017 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
The identification of ACVR1 as the causative gene for FOP now allows the genetic screening of FOP patients to identify the frequency of the identified recurrent ACVR1 mutation and to investigate genetic variability that may be associated with this severely debilitating disease.
|
18830232 |
2009 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
In this manuscript, we describe the molecular mechanism of the causative gene <i>ALK2</i> in FOP, mainly focusing on the prominent role of Activin A in HO.
|
31341010 |
2019 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
This repression was mostly overcome by specific suppression of ALK2 expression and treatment with an ALK2 inhibitor, indicating that the inhibition of iPSC generation and maintenance observed in FOP-derived skin fibroblasts results from constitutive activation of ALK2.
|
22949078 |
2012 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
An activating mutation in the BMP type I receptor ALK2 has been shown to contribute to the heterotopic lesions in FOP patients, yet recent studies have shown that other events are required to stimulate HO including activation of sensory neurons, mast cell degranulation, lymphocyte infiltration, skeletal myocyte cell death, and endothelial-mesenchymal transition (EndMT).
|
24796520 |
2014 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
The discovery that mildly activating mutations in ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor, is the cause of FOP has provided opportunities to identify previously unknown functions for this receptor and for BMP signaling and to develop new diagnostic and therapeutic strategies for FOP and other more common forms of heterotopic ossification, as well as tissue engineering applications.
|
21340697 |
2011 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
We describe seven novel deletions/translocations in five patients (including two with normal karyotype) whose breakpoints were PCR-validated and involved MACROD2, CACNA2D4, TET2, SGMS2, LRBA, SH3D19, INTS3, FOP (CHTOP), SCLT1, and PHF17.
|
23733509 |
2013 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
The episodic or sporadic nature of HO associated with FOP rests with the occurrence of specific 'triggers' that push the hypersensitive ALK2-FOP receptor into full signaling mode.
|
29128351 |
2018 |
|
Fibrodysplasia Ossificans Progressiva
|
1.000 |
Biomarker
|
disease |
BEFREE |
The diagnosis of FOP requires typical clinical manifestations or ACVR1 gene detection.
|
31529313 |
2020 |