Insights into the biology of fibrodysplasia ossificans progressiva using patient-derived induced pluripotent stem cells

Ashburn, 2004, Drug repositioning: identifying and developing new uses for existing drugs, Nat Rev Drug Discov, 3, 673, 10.1038/nrd1468 Morgan, 2011, The cost of drug development: a systematic review, Health Policy, 100, 4, 10.1016/j.healthpol.2010.12.002 DiMasi, 2003, The price of innovation: new estimates of drug development costs, J Health Econ, 22, 151, 10.1016/S0167-6296(02)00126-1 Sertkaya, 2016, Key cost drivers of pharmaceutical clinical trials in the United States, Clin Trials, 13, 117, 10.1177/1740774515625964 Paul, 2010, How to improve R&D productivity: the pharmaceutical industry's grand challenge, Nat Rev Drug Discov, 9, 203, 10.1038/nrd3078 Adams, 2010, Spending on new drug development1, Health Econ, 19, 130, 10.1002/hec.1454 DiMasi, 1995, Research and development costs for new drugs by therapeutic category. A study of the US pharmaceutical industry, Pharmacoeconomics, 7, 152, 10.2165/00019053-199507020-00007 Adams, 2006, Estimating the cost of new drug development: is it really 802 million dollars?, Health Aff, 25, 420, 10.1377/hlthaff.25.2.420 Watch C, Rx R&D Myths, 2001 Dimasi, 1995, R&D costs, innovative output and firm size in the pharmaceutical industry, Int J Econ Bus, 2, 201, 10.1080/758519309 DiMasi, 1991, Cost of innovation in the pharmaceutical industry, J Health Econ, 10, 107, 10.1016/0167-6296(91)90001-4 Lavecchia, 2013, Virtual screening strategies in drug discovery: a critical review, Curr Med Chem, 20, 2839, 10.2174/09298673113209990001 Ward, 2013, Decline in new drug launches: myth or reality? Retrospective observational study using 30–years of data from the UK, BMJ Open, 3, 10.1136/bmjopen-2012-002088 Scannell, 2012, Diagnosing the decline in pharmaceutical R&D efficiency, Nat Rev Drug Discov, 11, 191, 10.1038/nrd3681 Charlton, 2006, Why medical research needs a new specialty of 'pure medical science', Clin Med, 6, 163, 10.7861/clinmedicine.6-2-163 Wurtman, 1995, The slowing of treatment discovery, 1965-1995, Nat Med, 1, 1122, 10.1038/nm1195-1122 Takahashi, 2013, Induced pluripotent stem cells in medicine and biology, Development, 140, 2457, 10.1242/dev.092551 Takahashi, 2006, Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors, Cell, 126, 663, 10.1016/j.cell.2006.07.024 Takahashi, 2007, Induction of pluripotent stem cells from adult human fibroblasts by defined factors, Cell, 131, 861, 10.1016/j.cell.2007.11.019 Inoue, 2014, iPS cells: a game changer for future medicine, EMBO J, 33, 409, 10.1002/embj.201387098 Park, 2008, Disease-specific induced pluripotent stem cells, Cell, 134, 877, 10.1016/j.cell.2008.07.041 Dimos, 2008, Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons, Science, 321, 1218, 10.1126/science.1158799 Inoue, 2011, The use of induced pluripotent stem cells in drug development, Clin Pharmacol Ther, 89, 655, 10.1038/clpt.2011.38 Seok, 2013, Genomic responses in mouse models poorly mimic human inflammatory diseases, Proc Natl Acad Sci U S A, 110, 3507, 10.1073/pnas.1222878110 Takao, 2015, Genomic responses in mouse models greatly mimic human inflammatory diseases, Proc Natl Acad Sci U S A, 112, 1167, 10.1073/pnas.1401965111 Merkle, 2013, Modeling human disease with pluripotent stem cells: from genome association to function, Cell Stem Cell, 12, 656, 10.1016/j.stem.2013.05.016 Zhang, 2013, The phenotype and genotype of fibrodysplasia ossificans progressiva in China: a report of 72 cases, Bone, 57, 386, 10.1016/j.bone.2013.09.002 Kaplan, 2012, Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal metamorphosis, Dis Model Mech, 5, 756, 10.1242/dmm.010280 Shore, 2010, Inherited human diseases of heterotopic bone formation, Nat Rev Rheumatol, 6, 518, 10.1038/nrrheum.2010.122 Kaplan, 2007, Morphogen receptor genes and metamorphogenes: skeleton keys to metamorphosis, Ann N Y Acad Sci, 1116, 113, 10.1196/annals.1402.039 Pignolo, 2013, Fibrodysplasia ossificans progressiva: diagnosis, management, and therapeutic horizons, Pediatr Endocrinol Rev, 10, 437 Kaplan, 2008, Fibrodysplasia ossificans progressiva. Best practice & research, Clin Rheumatol, 22, 191 Mueller, 2012, Promiscuity and specificity in BMP receptor activation, FEBS Lett, 586, 1846, 10.1016/j.febslet.2012.02.043 Chaikuad, 2012, Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva, J Biol Chem, 287, 36990, 10.1074/jbc.M112.365932 Kaplan, 2009, Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1, Hum Mutat, 30, 379, 10.1002/humu.20868 Urist, 1965, Bone: formation by autoinduction, Science, 150, 893, 10.1126/science.150.3698.893 Wozney, 1988, Novel regulators of bone formation: molecular clones and activities, Science, 242, 1528, 10.1126/science.3201241 Matsumoto, 2013, Induced pluripotent stem cells from patients with human fibrodysplasia ossificans progressiva show increased mineralization and cartilage formation, Orphanet J Rare Dis, 8, 190, 10.1186/1750-1172-8-190 Hamasaki, 2012, Pathogenic mutation of ALK2 inhibits induced pluripotent stem cell reprogramming and maintenance: mechanisms of reprogramming and strategy for drug identification, Stem Cell, 30, 2437, 10.1002/stem.1221 Fukuda, 2008, A unique mutation of ALK2, G356D, found in a patient with fibrodysplasia ossificans progressiva is a moderately activated BMP type I receptor, Biochem Biophys Res Commun, 377, 905, 10.1016/j.bbrc.2008.10.093 Fukuda, 2009, Constitutively activated ALK2 and increased SMAD1/5 cooperatively induce bone morphogenetic protein signaling in fibrodysplasia ossificans progressiva, J Biol Chem, 284, 7149, 10.1074/jbc.M801681200 Shen, 2009, The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization, J Clin Investig, 119, 3462 Song, 2010, Molecular consequences of the ACVR1(R206H) mutation of fibrodysplasia ossificans progressiva, J Biol Chem, 285, 22542, 10.1074/jbc.M109.094557 van Dinther, 2010, ALK2 R206H mutation linked to fibrodysplasia ossificans progressiva confers constitutive activity to the BMP type I receptor and sensitizes mesenchymal cells to BMP-induced osteoblast differentiation and bone formation, J Bone Miner Res, 25, 1208 Ohte, 2011, A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H, Biochem Biophys Res Commun, 407, 213, 10.1016/j.bbrc.2011.03.001 Le, 2012, Hyperactive BMP signaling induced by ALK2(R206H) requires type II receptor function in a Drosophila model for classic fibrodysplasia ossificans progressiva, Dev Dynam, 241, 200, 10.1002/dvdy.22779 Bagarova, 2013, Constitutively active ALK2 receptor mutants require type II receptor cooperation, Mol Cell Biol, 33, 2413, 10.1128/MCB.01595-12 Chakkalakal, 2012, An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva, J Bone Miner Res, 27, 1746, 10.1002/jbmr.1637 Culbert, 2014, Alk2 regulates early chondrogenic fate in fibrodysplasia ossificans progressiva heterotopic endochondral ossification, Stem Cell, 32, 1289, 10.1002/stem.1633 Billings, 2008, Dysregulated BMP signaling and enhanced osteogenic differentiation of connective tissue progenitor cells from patients with fibrodysplasia ossificans progressiva (FOP), J Bone Miner Res, 23, 305, 10.1359/jbmr.071030 Pignolo, 2016, The natural history of flare-ups in fibrodysplasia ossificans progressiva (FOP): a comprehensive global assessment, J Bone Miner Res, 31, 650, 10.1002/jbmr.2728 Kim, 2010, Epigenetic memory in induced pluripotent stem cells, Nature, 467, 285, 10.1038/nature09342 Chai, 2000, Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis, Development, 127, 1671, 10.1242/dev.127.8.1671 Tickle, 2015, How the embryo makes a limb: determination, polarity and identity, J Anat, 227, 418 Gros, 2014, Vertebrate limb bud formation is initiated by localized epithelial-to-mesenchymal transition, Science, 343, 1253, 10.1126/science.1248228 Evans, 2006, Spatial relations between avian craniofacial neural crest and paraxial mesoderm cells, Dev Dynam, 235, 1310, 10.1002/dvdy.20663 Noden, 1983, The role of the neural crest in patterning of avian cranial skeletal, connective, and muscle tissues, Dev Biol, 96, 144, 10.1016/0012-1606(83)90318-4 Noden, 2005, Relations and interactions between cranial mesoderm and neural crest populations, J Anat, 207, 575 Jiang, 2002, Tissue origins and interactions in the mammalian skull vault, Dev Biol, 241, 106, 10.1006/dbio.2001.0487 Mishina, 2014, Neural crest cell signaling pathways critical to cranial bone development and pathology, Exp Cell Res, 325, 138, 10.1016/j.yexcr.2014.01.019 Umeda, 2012, Human chondrogenic paraxial mesoderm, directed specification and prospective isolation from pluripotent stem cells, Sci Rep, 2, 455, 10.1038/srep00455 Menendez, 2013, Directed differentiation of human pluripotent cells to neural crest stem cells, Nat Protoc, 8, 203, 10.1038/nprot.2012.156 Lee, 2007, Isolation and directed differentiation of neural crest stem cells derived from human embryonic stem cells, Nat Biotechnol, 25, 1468, 10.1038/nbt1365 Umeda, 2015, Long-term expandable SOX9+ chondrogenic ectomesenchymal cells from human pluripotent stem cells, Stem Cell Reports, 4, 712, 10.1016/j.stemcr.2015.02.012 Loh, 2016, Mapping the pairwise choices leading from pluripotency to human bone, heart, and other mesoderm cell types, Cell, 166, 451, 10.1016/j.cell.2016.06.011 Nakajima, 2019, Somitogenesis method based on human pluripotent stem cells for in vitro generation of somite derivatives, JoVE, 10.3791/59359 Nakajima, 2018, Modeling human somite development and fibrodysplasia ossificans progressiva with induced pluripotent stem cells, Development, 145, 10.1242/dev.165431 Fukuta, 2014, Derivation of mesenchymal stromal cells from pluripotent stem cells through a neural crest lineage using small molecule compounds with defined media, PLoS One, 9, 10.1371/journal.pone.0112291 Matsumoto, 2015, New protocol to optimize iPS cells for genome analysis of fibrodysplasia ossificans progressiva, Stem Cell, 33, 1730, 10.1002/stem.1981 Hino, 2015, Neofunction of ACVR1 in fibrodysplasia ossificans progressiva, Proc Natl Acad Sci USA, 112, 15438, 10.1073/pnas.1510540112 Shore, 2006, A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva, Nat Genet, 38, 525, 10.1038/ng1783 Hatsell, 2015, ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A, Sci Transl Med, 7, 303ra137, 10.1126/scitranslmed.aac4358 Yu, 2008, BMP type I receptor inhibition reduces heterotopic [corrected] ossification, Nat Med, 14, 1363, 10.1038/nm.1888 Yu, 2008, Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism, Nat Chem Biol, 4, 33, 10.1038/nchembio.2007.54 Shimono, 2011, Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-gamma agonists, Nat Med, 17, 454, 10.1038/nm.2334 Agarwal, 2016, Inhibition of Hif1alpha prevents both trauma-induced and genetic heterotopic ossification, Proc Natl Acad Sci U S A, 113, E338, 10.1073/pnas.1515397113 Hino, 2017, Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in fibrodysplasia ossificans progressiva, J Clin Investig, 127, 3339, 10.1172/JCI93521 Chen, 2014, mTORC1 signaling controls mammalian skeletal growth through stimulation of protein synthesis, Development (Camb), 141, 2848, 10.1242/dev.108811 Lim, 2016, Dual function of Bmpr1a signaling in restricting preosteoblast proliferation and stimulating osteoblast activity in mouse, Development, 143, 339, 10.1242/dev.126227 Hino, 2018, An mTOR signaling modulator suppressed heterotopic ossification of fibrodysplasia ossificans progressiva, Stem Cell Reports, 11, 1106, 10.1016/j.stemcr.2018.10.007 Oprea, 2011, Drug repurposing from an academic perspective, Drug Discov Today Ther Strateg, 8, 61, 10.1016/j.ddstr.2011.10.002 Yamashita, 2014, Statin treatment rescues FGFR3 skeletal dysplasia phenotypes, Nature, 513, 507, 10.1038/nature13775 Imamura, 2017, The Src/c-Abl pathway is a potential therapeutic target in amyotrophic lateral sclerosis, Sci Transl Med, 9, 10.1126/scitranslmed.aaf3962 Hosoya, 2017, Cochlear cell modeling using disease-specific iPSCs unveils a degenerative phenotype and suggests treatments for congenital progressive hearing loss, Cell Rep, 18, 68, 10.1016/j.celrep.2016.12.020