Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva

被引:0
作者
Zhou, Yijun [1 ,3 ]
Shi, Ce [2 ,3 ]
Sun, Hongchen [2 ,3 ]
机构
[1] Jilin Univ, Hosp Stomatol, Dept Endodont, Changchun 130021, Peoples R China
[2] Jilin Univ, Hosp Stomatol, Dept Oral Pathol, Changchun 130021, Peoples R China
[3] Jilin Univ, Jilin Prov Key Lab Tooth Dev & Bone Remodeling, Changchun 130021, Peoples R China
基金
中国国家自然科学基金;
关键词
Fibrodysplasia ossificans progressiva (FOP); Heterotopic ossification (HO); Mechanism; Drug treatment; Activin A receptor type 1 (ACVR1); HETEROTOPIC OSSIFICATION; BONE-FORMATION; INHIBITION; DORSOMORPHIN; CELLS; DIFFERENTIATION; MANAGEMENT; IMATINIB; MUTATION; AGONIST;
D O I
10.1631/jzus.B2300779
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by congenital bilateral malformation of the large toe and progressive, extensive, and irreversible heterotopic ossification (HO) of soft tissues throughout the body, leading to severe disabilities. FOP is caused primarily by mutations in activin A receptor type 1 (ACVR1), also known as activin-like kinase 2 (ALK2), which encodes a receptor belonging to the bone morphogenetic protein (BMP) type I family. However, the continuous and complex process of HO in FOP is not yet fully understood, which has impeded the development of therapeutic drugs. Despite surgical removal of HO, which often results in recurrence and expansion of ossification, there is currently no definitive drug treatment available to completely prevent, halt, or reverse the progression of HO in FOP. Currently, researchers are intensively studying the pathogenesis of FOP at various stages and developing promising drug candidates, including saracatinib, palovarotene, and rapamycin. This review provides an overview of progress in understanding the mechanism of FOP and the development of therapeutic drugs, with the goal of providing insights for further research and the development of new treatment methods.
引用
收藏
页码:317 / 332
页数:16
相关论文
共 108 条
[1]   Inhibition of phosphatidylinositol 3-kinase α (PI3Kα) prevents heterotopic ossification [J].
Antonio Valer, Jose ;
Sanchez-de-Diego, Cristina ;
Gamez, Beatriz ;
Mishina, Yuji ;
Luis Rosa, Jose ;
Ventura, Francesc .
EMBO MOLECULAR MEDICINE, 2019, 11 (09)
[2]   Anti-ACVR1 antibodies exacerbate heterotopic ossification in fibrodysplasia ossificans progressiva (FOP) by activating FOP-mutant ACVR1 [J].
Aykul, Senem ;
Huang, Lily ;
Wang, Lili ;
Das, Nanditha M. ;
Reisman, Sandra ;
Ray, Yonaton ;
Zhang, Qian ;
Rothman, Nyanza ;
Nannuru, Kalyan C. ;
Kamat, Vishal ;
Brydges, Susannah ;
Troncone, Luca ;
Johnsen, Laura ;
Yu, Paul B. ;
Fazio, Sergio ;
Lees-Shepard, John ;
Schutz, Kevin ;
Murphy, Andrew J. ;
Economides, Aris N. ;
Idone, Vincent ;
Hatsell, Sarah J. .
JOURNAL OF CLINICAL INVESTIGATION, 2022, 132 (12)
[3]   Activin A forms a non-signaling complex with ACVR1 and type II Activin/BMP receptors via its finger 2 tip loop [J].
Aykul, Senem ;
Corpina, Richard A. ;
Goebel, Erich J. ;
Cunanan, Camille J. ;
Dimitriou, Alexandra ;
Kim, Hyon Jong ;
Zhang, Qian ;
Rafique, Ashique ;
Leidich, Raymond ;
Wang, Xin ;
McClain, Joyce ;
Jimenez, Johanna ;
Nannuru, Kalyan C. ;
Rothman, Nyanza J. ;
Lees-Shepard, John B. ;
Martinez-Hackert, Erik ;
Murphy, Andrew J. ;
Thompson, Thomas B. ;
Economides, Aris N. ;
Idonel, Vincent .
ELIFE, 2020, 9 :1-19
[4]   E6201, an intravenous MEK1 inhibitor, achieves an exceptional response in BRAF V600E-mutated metastatic malignant melanoma with brain metastases [J].
Babiker, Hani M. ;
Byron, Sara A. ;
Hendricks, William P. D. ;
Elmquist, William F. ;
Gampa, Gautham ;
Vondrak, Jessica ;
Aldrich, Jessica ;
Cuyugan, Lori ;
Adkins, Jonathan ;
De Luca, Valerie ;
Tibes, Raoul ;
Borad, Mitesh J. ;
Marceau, Katie ;
Myers, Thomas J. ;
Paradiso, Linda J. ;
Liang, Winnie S. ;
Korn, Ronald L. ;
Cridebring, Derek ;
Von Hoff, Daniel D. ;
Carpten, John D. ;
Craig, David W. ;
Trent, Jeffrey M. ;
Gordon, Michael S. .
INVESTIGATIONAL NEW DRUGS, 2019, 37 (04) :636-645
[5]   NF-κB/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification [J].
Barruet, Emilie ;
Morales, Blanca M. ;
Cain, Corey J. ;
Ton, Amy N. ;
Wentworth, Kelly L. ;
Chan, Tea, V ;
Moody, Tania A. ;
Haks, Marielle C. ;
Ottenhoff, Tom H. M. ;
Hellman, Judith ;
Nakamura, Mary C. ;
Hsiao, Edward C. .
JCI INSIGHT, 2018, 3 (22)
[6]  
Blueprint Medicines Corporation, 2019, SAFETY TOLERABILITY
[7]   Mast cell inhibition as a therapeutic approach in fibrodysplasia ossificans progressiva (FOP) [J].
Brennan, Tracy A. ;
Lindborg, Carter M. ;
Bergbauer, Christian R. ;
Wang, Haitao ;
Kaplan, Frederick S. ;
Pignolo, Robert J. .
BONE, 2018, 109 :259-266
[8]   Induced Pluripotent Stem Cells to Model Human Fibrodysplasia Ossificans Progressiva [J].
Cai, Jie ;
Orlova, Valeria V. ;
Cai, Xiujuan ;
Eekhoff, Elisabeth M. W. ;
Zhang, Keqin ;
Pei, Duanqing ;
Pan, Guangjin ;
Mummery, Christine L. ;
ten Dijke, Peter .
STEM CELL REPORTS, 2015, 5 (06) :963-970
[9]   Glivec (ST1571, Imatinib), a rationally developed, targeted anticancer drug [J].
Capdeville, R ;
Buchdunger, E ;
Zimmermann, J ;
Matter, A .
NATURE REVIEWS DRUG DISCOVERY, 2002, 1 (07) :493-502
[10]   Structure of the Bone Morphogenetic Protein Receptor ALK2 and Implications for Fibrodysplasia Ossificans Progressiva [J].
Chaikuad, Apirat ;
Alfano, Ivan ;
Kerr, Georgina ;
Sanvitale, Caroline E. ;
Boergermann, Jan H. ;
Triffitt, James T. ;
von Delft, Frank ;
Knapp, Stefan ;
Knaus, Petra ;
Bullock, Alex N. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (44) :36990-36998