Cited by 358Pharmaceutical Economics and PolicyGenomics and Rare DiseasesStatistical Methods in Clinical Trials

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Therapies for rare diseases: therapeutic modalities, progress and challenges ahead

Tambuyzer, Erik, Vandendriessche, Benjamin, Austin, Christopher P., Brooks, Philip J., Larsson, Kristina, Miller Needleman, Katherine I., Valentine, James, Davies, Kay, Groft, Stephen C., Preti, Robert, Oprea, Tudor I., Prunotto, Marco·2020·Nature Reviews Drug Discovery

DOI 10.1038/s41573-019-0049-9

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Abstract

Most rare diseases still lack approved treatments despite major advances in research providing the tools to understand their molecular basis, as well as legislation providing regulatory and economic incentives to catalyse the development of specific therapies. Addressing this translational gap is a multifaceted challenge, for which a key aspect is the selection of the optimal therapeutic modality for translating advances in rare disease knowledge into potential medicines, known as orphan drugs. With this in mind, we discuss here the technological basis and rare disease applicability of the main therapeutic modalities, including small molecules, monoclonal antibodies, protein replacement therapies, oligonucleotides and gene and cell therapies, as well as drug repurposing. For each modality, we consider its strengths and limitations as a platform for rare disease therapy development and describe clinical progress so far in developing drugs based on it. We also discuss selected overarching topics in the development of therapies for rare diseases, such as approval statistics, engagement of patients in the process, regulatory pathways and digital tools.

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Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00129-0 · Cited by 18,139
Continuous cultures of fused cells secreting antibody of predefined specificity
Köhler, G., & Milstein, C. (1975) · Nature · doi:10.1038/256495a0 · Cited by 17,200
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(96)00423-1 · Cited by 11,484
Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework
Biomarkers Definitions Working Group (2001) · Clinical Pharmacology & Therapeutics · doi:10.1067/mcp.2001.113989 · Cited by 6,771
Drug repurposing: progress, challenges and recommendations
Pushpakom, S., Iorio, F., Eyers, P. A., Escott, K. J., Hopper, S., Wells, A., Doig, A., Guilliams, T., Latimer, J., McNamee, C., et al. (2019) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.168 · Cited by 4,718
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.09.019 · Cited by 3,720
Update on Key Emerging Challenges in Cystic Fibrosis
Jennings, M. T., Riekert, K. A., & Boyle, M. (2014) · Medical Principles and Practice · doi:10.1159/000357646 · Cited by 3,671
Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis
Adams, D., Gonzalez-Duarte, A., O’Riordan, W. D., Yang, C.-C., Ueda, M., Kristen, A. V., Tournev, I., Schmidt, H. H., Coelho, T., Berk, J. L., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1716153 · Cited by 3,047
Rapid generation of functional human IgG antibodies derived from Fab-on-phage display libraries
Jostock, T., Vanhove, M., Brepoels, E., van Gool, R., Daukandt, M., Wehnert, A., van Hegelsom, R., Dransfield, D., Sexton, D., Devlin, M., et al. (2004) · Journal of Immunological Methods · doi:10.1016/j.jim.2004.03.014 · Cited by 2,572
Sildenafil Citrate Therapy for Pulmonary Arterial Hypertension
Galiè, N., Ghofrani, H. A., Torbicki, A., Barst, R. J., Rubin, L. J., Badesch, D. B., Fleming, T. R., Parpia, T., Burgess, G., Branzi, A., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050010 · Cited by 2,466
Adeno-associated virus vector as a platform for gene therapy delivery
Wang, D., Tai, P. W. L., & Gao, G. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0012-9 · Cited by 2,444
A comprehensive map of molecular drug targets
Santos, R., Ursu, O., Gaulton, A., Bento, A. P., Donadi, R. S., Bologa, C. G., Karlsson, A., Al-Lazikani, B., Hersey, A., Oprea, T. I., et al. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.230 · Cited by 2,427
Self-citation
Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy
Mendell, J. R., Al-Zaidy, S., Shell, R., Arnold, W. D., Rodino-Klapac, L. R., Prior, T. W., Lowes, L., Alfano, L., Berry, K., Church, K., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1706198 · Cited by 2,381
What are biomarkers?
Strimbu, K., & Tavel, J. A. (2010) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0b013e32833ed177 · Cited by 2,062
Diagnosing the decline in pharmaceutical R&D efficiency
Scannell, J. W., Blanckley, A., Boldon, H., & Warrington, B. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3681 · Cited by 1,981
Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery
Zufferey, R., Dull, T., Mandel, R. J., Bukovsky, A., Quiroz, D., Naldini, L., & Trono, D. (1998) · Journal of Virology · doi:10.1128/jvi.72.12.9873-9880.1998 · Cited by 1,815
Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database
Nguengang Wakap, S., Lambert, D. M., Olry, A., Rodwell, C., Gueydan, C., Lanneau, V., Murphy, D., Le Cam, Y., & Rath, A. (2020) · European Journal of Human Genetics · doi:10.1038/s41431-019-0508-0 · Cited by 1,752
Federal Communications Commission
Schultz, D., & Vile, J. R. (2015) · Routledge eBooks · doi:10.4324/9781315699868-248 · Cited by 1,555
Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy
Cartier, N., Hacein-Bey-Abina, S., Bartholomae, C. C., Veres, G., Schmidt, M., Kutschera, I., Vidaud, M., Abel, U., Dal-Cortivo, L., Caccavelli, L., et al. (2009) · Science · doi:10.1126/science.1171242 · Cited by 1,508
Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis
Benson, M. D., Waddington‐Cruz, M., Berk, J. L., Polydefkis, M. J., Dyck, P. J. B., Wang, A. K., Planté‐Bordeneuve, V., Barroso, F. A., Merlini, G., Obici, L. P., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1716793 · Cited by 1,483
The current state and future directions of RNAi-based therapeutics
Setten, R. L., Rossi, J. J., & Han, S.-P. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0017-4 · Cited by 1,443
Induced pluripotent stem cells from a spinal muscular atrophy patient
Ebert, A. D., Yu, J., Rose, F. F., Mattis, V. B., Lorson, C. L., Thomson, J. A., & Svendsen, C. N. (2009) · Nature · doi:10.1038/nature07677 · Cited by 1,441
Therapeutic antibodies: successes, limitations and hopes for the future
Chames, P., Van Regenmortel, M., Weiss, E., & Baty, D. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00190.x · Cited by 1,382
The therapeutic monoclonal antibody market
Ecker, D. M., Jones, S. D., & Levine, H. L. (2014) · mAbs · doi:10.4161/19420862.2015.989042 · Cited by 1,369
Impact of high-throughput screening in biomedical research
Macarron, R., Banks, M. N., Bojanic, D., Burns, D. J., Cirovic, D. A., Garyantes, T., Green, D. V. S., Hertzberg, R. P., Janzen, W. P., Paslay, J. W., et al. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3368 · Cited by 1,364
Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770
Goor, F. V., Hadidaꝉ, S., Grootenhuis, P. D. J., Burton, B., Cao, D., Neuberger, T., Turnbull, A., Singh, A. K., Joubran, J., Hazlewood, A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904709106 · Cited by 1,225
The chemical evolution of oligonucleotide therapies of clinical utility
Khvorova, A., & Watts, J. K. (2017) · Nature Biotechnology · doi:10.1038/nbt.3765 · Cited by 1,216
Making antibody fragments using phage display libraries
Clackson, T., Hoogenboom, H. R., Griffiths, A. D., & Winter, G. P. (1991) · Nature · doi:10.1038/352624a0 · Cited by 1,211
Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy
Biffi, A., Montini, E., Lorioli, L., Cesani, M., Fumagalli, F., Plati, T., Baldoli, C., Martino, S., Calabria, A., Canale, S., et al. (2013) · Science · doi:10.1126/science.1233158 · Cited by 1,180
PTC124 targets genetic disorders caused by nonsense mutations
Welch, E. M., Barton, E. R., Zhuo, J., Tomizawa, Y., Friesen, W. J., Trifillis, P., Paushkin, S. V., Patel, M., Trotta, C. R., Hwang, S., et al. (2007) · Nature · doi:10.1038/nature05756 · Cited by 1,175
Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809
Van Goor, F., Hadida, S., Grootenhuis, P. D. J., Burton, B., Stack, J. H., Straley, K. S., Decker, C. J., Miller, M., McCartney, J., Olson, E. R., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105787108 · Cited by 1,088
Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders
Jeffrey Conn, P., Christopoulos, A., & Lindsley, C. W. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2760 · Cited by 1,063
The Drug Repurposing Hub: a next-generation drug library and information resource
Corsello, S. M., Bittker, J. A., Liu, Z., Gould, J., McCarren, P. R., Hirschman, J., Johnston, S. E., Vrcic, A., Wong, B., Khan, M., et al. (2017) · Nature Medicine · doi:10.1038/nm.4306 · Cited by 1,028
Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura
Scully, M., Cataland, S. R., Peyvandi, F., Coppo, P., Knöbl, P., Hovinga, J. A. K., Metjian, A. D., de la Rubia, J., Pavenski, K., Callewaert, F., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1806311 · Cited by 1,027
Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome
Aiuti, A., Biasco, L., Scaramuzza, S., Ferrua, F., Cicalese, M. P., Baricordi, C., Dionisio, F., Calabria, A., Giannelli, S., Castiello, M. C., et al. (2013) · Science · doi:10.1126/science.1233151 · Cited by 1,025
Opportunities and challenges in phenotypic drug discovery: an industry perspective
Moffat, J. G., Vincent, F., Lee, J. A., Eder, J., & Prunotto, M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.111 · Cited by 939
Self-citation
Emerging issues in AAV-mediated in vivo gene therapy
Colella, P., Ronzitti, G., & Mingozzi, F. (2018) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2017.11.007 · Cited by 881
Antisense oligonucleotides: the next frontier for treatment of neurological disorders
Rinaldi, C., & Wood, M. J. A. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.148 · Cited by 788
Next generation antibody drugs: pursuit of the 'high-hanging fruit'
Carter, P. J., & Lazar, G. A. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.227 · Cited by 780
Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors
Mahlangu, J. N., Oldenburg, J., Paz‐Priel, I., Négrier, C., Niggli, M., Mancuso, M. E., Schmitt, C., Jiménez‐Yuste, V., Kempton, C. L., Dhalluin, C., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1803550 · Cited by 777
Antisense oligonucleotides: basic concepts and mechanisms.
Dias, N., & Stein, C. A. (2002) · PubMed · Cited by 759
Identifying facial phenotypes of genetic disorders using deep learning
Gurovich, Y., Hanani, Y., Bar, O., Nadav, G., Fleischer, N., Gelbman, D., Basel-Salmon, L., Krawitz, P. M., Kamphausen, S. B., Zenker, M., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0279-0 · Cited by 739
VX-445–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles
Keating, D., Marigowda, G., Burr, L., Daines, C., Mall, M. A., McKone, E. F., Ramsey, B. W., Rowe, S. M., Sass, L. A., Tullis, E., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1807120 · Cited by 726
Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia
Thompson, A. A., Walters, M. C., Kwiatkowski, J., Rasko, J. E. J., Ribeil, J.-A., Hongeng, S., Magrin, E., Schiller, G. J., Payen, E., Semeraro, M., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1705342 · Cited by 684
Non-invasive delivery strategies for biologics
Anselmo, A. C., Gokarn, Y. R., & Mitragotri, S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.183 · Cited by 671
Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond
Ghofrani, H. A., Osterloh, I. H., & Grimminger, F. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2030 · Cited by 632
Replacement Therapy for Alpha1-Antitrypsin Deficiency Associated with Emphysema
Wewers, M. D., Casolaro, M. A., Sellers, S. E., Swayze, S. C., McPhaul, K. M., Wittes, J. T., & Crystal, R. G. (1987) · New England Journal of Medicine · doi:10.1056/nejm198704233161704 · Cited by 631
Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy
Eichler, F., Duncan, C., Musolino, P. L., Orchard, P. J., De Oliveira, S., Thrasher, A. J., Armant, M., Dansereau, C., Lund, T. C., Miller, W. P., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1700554 · Cited by 604
Delivery technologies for genome editing
Yin, H., Kauffman, K. J., & Anderson, D. G. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.280 · Cited by 597
Lipid nanoparticles enabling gene therapies: from concepts to clinical utility
Kulkarni, J. A., Cullis, P. R., & van der Meel, R. (2018) · Nucleic Acid Therapeutics · doi:10.1089/nat.2018.0721 · Cited by 592
Efficacy and safety of rilonacept (interleukin‐1 trap) in patients with cryopyrin‐associated periodic syndromes: Results from two sequential placebo‐controlled studies
Hoffman, H. M., Throne, M. L., Amar, N. J., Sebai, M., Kivitz, A. J., Kavanaugh, A., Weinstein, S. P., Belomestnov, P., Yancopoulos, G. D., Stahl, N., et al. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23687 · Cited by 577
How many rare diseases are there?
Haendel, M., Vasilevsky, N., Unni, D., Bologa, C., Harris, N., Rehm, H., Hamosh, A., Baynam, G., Groza, T., McMurry, J., et al. (2020) · Nature Reviews Drug Discovery · doi:10.1038/d41573-019-00180-y · Cited by 554 · cited 1×
“level terms) available from the analysis described in reF.(153) and the number of orphan drugs receiving approval by the FDA”
MethodSelf-citation
Self-inactivating retroviral vectors designed for transfer of whole genes into mammalian cells.
Yu, S. F., von Rüden, T., Kantoff, P. W., Garber, C., Seiberg, M., Rüther, U., Anderson, W. F., Wagner, E. F., & Gilboa, E. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.10.3194 · Cited by 540
A Dictionary of Epidemiology (DRAFT)
(2014) · doi:10.1093/acref/9780199976720.001.0001 · Cited by 530
Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes
Benedetti, F. D., Gattorno, M., Antón, J., Ben‐Chetrit, E., Frenkel, J., Hoffman, H. M., Koné‐Paut, I., Lachmann, H. J., Özen, S., Simon, A., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1706314 · Cited by 496
The Matchmaker Exchange: A Platform for Rare Disease Gene Discovery
Philippakis, A., Azzariti, D. R., Beltrán, S., Brookes, A. J., Brownstein, C. A., Brudno, M., Brunner, H. G., Buske, O. J., Carey, K., Doll, C., et al. (2015) · Human Mutation · doi:10.1002/humu.22858 · Cited by 477
The Increasingly Human and Profitable Monoclonal Antibody Market
Grilo, A. L., & Mantalaris, A. (2018) · Trends in biotechnology · doi:10.1016/j.tibtech.2018.05.014 · Cited by 468
Rapid generation of fully human monoclonal antibodies specific to a vaccinating antigen
Smith, K., Garman, L., Wrammert, J., Zheng, N., Capra, J. D., Ahmed, R., & Wilson, P. C. (2009) · Nature Protocols · doi:10.1038/nprot.2009.3 · Cited by 467
Two Decades under the Influence of the Rule of Five and the Changing Properties of Approved Oral Drugs
Shultz, M. D. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00686 · Cited by 466
Endgame: Glybera Finally Recommended for Approval as the First Gene Therapy Drug in the European Union
Ylä‐Herttuala, S. (2012) · Molecular Therapy · doi:10.1038/mt.2012.194 · Cited by 465
Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization
Farnaes, L., Hildreth, A., Sweeney, N. M., Clark, M. M., Chowdhury, S., Nahas, S., Cakici, J. A., Benson, W., Kaplan, R. H., Kronick, R., et al. (2018) · npj Genomic Medicine · doi:10.1038/s41525-018-0049-4 · Cited by 445
The NCGC Pharmaceutical Collection: A Comprehensive Resource of Clinically Approved Drugs Enabling Repurposing and Chemical Genomics
Huang, R., Southall, N. T., Wang, Y., Yasgar, A., Shinn, P., Jadhav, A., Nguyễn, Ð.-T., & Austin, C. P. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3001862 · Cited by 400
Self-citation
New Modalities for Challenging Targets in Drug Discovery
Valeur, E., Guéret, S. M., Adihou, H., Gopalakrishnan, R., Lemurell, M., Waldmann, H., Grossmann, T. N., & Plowright, A. T. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201611914 · Cited by 394
Anakinra, a recombinant human interleukin‐1 receptor antagonist (r‐metHuIL‐1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo‐controlled trial
Fleischmann, R., Schechtman, J., Bennett, R., Handel, M. L., Burmester, G. R., Tesser, J., Modafferi, D., Poulakos, J. J., & Sun, G. (2003) · Arthritis & Rheumatism · doi:10.1002/art.10870 · Cited by 392
Unexplored therapeutic opportunities in the human genome
Oprea, T. I., Bologa, C. G., Brunak, S., Campbell, A., Gan, G. N., Gaulton, A., Gomez, S. M., Guha, R., Hersey, A., Holmes, J., et al. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.14 · Cited by 378
Self-citation
Drug repurposing from an academic perspective
Oprea, T. I., Bauman, J. E., Bologa, C., Buranda, T., Chigaev, A., Edwards, B. S., Jarvik, J. W., Gresham, H. D., Haynes, M. K., Hjelle, B. L., et al. (2011) · Drug Discovery Today Therapeutic Strategies · doi:10.1016/j.ddstr.2011.10.002 · Cited by 364
Self-citation
In vivo tissue-tropism of adeno-associated viral vectors
Srivastava, A. (2016) · Current Opinion in Virology · doi:10.1016/j.coviro.2016.08.003 · Cited by 346
Antibody–Drug Conjugates for Cancer Treatment
Lambert, J. M., & Berkenblit, A. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-061516-121357 · Cited by 315
Replacement Therapy for Inherited Enzyme Deficiency
Brady, R. O., Tallman, J. F., Johnson, W. G., Gal, A. E., Leahy, W. R., Quirk, J. M., & Dekaban, A. S. (1973) · New England Journal of Medicine · doi:10.1056/nejm197307052890103 · Cited by 310
Therapeutics Based on Stop Codon Readthrough
Keeling, K. M., Xue, X., Gunn, G., & Bedwell, D. M. (2014) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-091212-153527 · Cited by 306
Gene therapy for neurological disorders: progress and prospects
Deverman, B. E., Ravina, B. M., Bankiewicz, K. S., Paul, S. M., & Sah, D. W. Y. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.110 · Cited by 306
Erratum: Unexplored therapeutic opportunities in the human genome
Oprea, T. I., Bologa, C., Brunak, S., Campbell, A., Gan, G. N., Gaulton, A., Gomez, S. M., Guha, R., Hersey, A., Holmes, J., et al. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.52 · Cited by 303
Self-citation
Bispecific antibodies: design, therapy, perspectives
Sedykh, S. E., Prinz, V. Y., Buneva, V. N., & Nevinsky, G. A. (2018) · Drug Design Development and Therapy · doi:10.2147/dddt.s151282 · Cited by 297
Access to Orphan Drugs: A Comprehensive Review of Legislations, Regulations and Policies in 35 Countries
Gammie, T. M., Lu, C. Y., & Babar, Z. U. (2015) · PLoS ONE · doi:10.1371/journal.pone.0140002 · Cited by 296
Replacement Therapy for Inherited Enzyme Deficiency
Brady, R. O., Pentchev, P. G., Gal, A. E., Hibbert, S. R., & Dekaban, A. S. (1974) · New England Journal of Medicine · doi:10.1056/nejm197411072911901 · Cited by 294
Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics
Räth, T., Baker, K., Dumont, J. A., Peters, R., Jiang, H., Qiao, S., Lencer, W. I., Pierce, G. F., & Blumberg, R. S. (2013) · Critical Reviews in Biotechnology · doi:10.3109/07388551.2013.834293 · Cited by 289
Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency
Ravin, S. S. D., Wu, X., Moir, S. L., Kardava, L., Anaya‐O’Brien, S., Kwatemaa, N., Littel, P. L., Theobald, N., Choi, U., Su, L., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad8856 · Cited by 284
Pharos: collating protein information to shed light on the druggable genome
Nguyen, D.-T., Mathias, S., Bologa, C., Brunak, S., Fernandez, N., Gaulton, A., Hersey, A., Holmes, J., Jensen, L. J., Karlsson, A., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw1072 · Cited by 279
Self-citation
Replacement therapy of alpha 1-antitrypsin deficiency. Reversal of protease-antiprotease imbalance within the alveolar structures of PiZ subjects.
Gadek, J. E., Klein, H., Holland, P. V., & Crystal, R. G. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110360 · Cited by 277
Impact of remote patient monitoring on clinical outcomes: An updated meta-analysis of randomized controlled trials
Noah, B., Keller, M. S., Mosadeghi, S., Stein, L., Johl, S., Delshad, S., Tashjian, V. C., Lew, D., Kwan, J. T., Jusufagic, A., et al. (2018) · npj Digital Medicine · doi:10.1038/s41746-017-0002-4 · Cited by 273
Enzyme Replacement Therapy for Lysosomal Diseases: Lessons from 20 Years of Experience and Remaining Challenges
Desnick, R. J., & Schuchman, E. H. (2012) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-090711-163739 · Cited by 268
Gene therapy for ADA‐SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products
Aiuti, A., Roncarolo, M. G., & Naldini, L. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201707573 · Cited by 264
Patient reported outcome measures in rare diseases: a narrative review
Slade, A. L., Isa, F., Kyte, D. G., Pankhurst, T., Kerecuk, L., Ferguson, J., Lipkin, G. W., & Calvert, M. (2018) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-018-0810-x · Cited by 258
Emptying the stores: lysosomal diseases and therapeutic strategies
Platt, F. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.214 · Cited by 257
Evolving trends in mAb production processes
Shukla, A. A., Wolfe, L. S., Mostafa, S. S., & Norman, C. (2017) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10061 · Cited by 250
Erratum: Gene therapy for neurological disorders: progress and prospects
Deverman, B. E., Ravina, B. M., Bankiewicz, K. S., Paul, S. M., & Sah, D. W. Y. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.158 · Cited by 248
Advances in therapy for spinal muscular atrophy: promises and challenges
Groen, E. J. N., Talbot, K., & Gillingwater, T. H. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2018.4 · Cited by 241
Sustained Benefit from Ivacaftor Demonstrated by Combining Clinical Trial and Cystic Fibrosis Patient Registry Data
Sawicki, G. S., McKone, E. F., Pasta, D. J., Millar, S. J., Wagener, J. S., Johnson, C. A., & Konstan, M. W. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201503-0578oc · Cited by 236
Chemical probes and drug leads from advances in synthetic planning and methodology
Gerry, C. J., & Schreiber, S. L. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.53 · Cited by 232
Recombinant Adeno-Associated Viral Integration and Genotoxicity: Insights from Animal Models
Chandler, R. J., Sands, M. S., & Venditti, C. P. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.009 · Cited by 211
Challenges of developing and conducting clinical trials in rare disorders
Kempf, L., Goldsmith, J. C., & Temple, R. (2017) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.38413 · Cited by 210
Organoids for Drug Discovery and Personalized Medicine
Takahashi, T. (2018) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010818-021108 · Cited by 210
Use and application of 3D-organoid technology
Artegiani, B., & Clevers, H. C. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy187 · Cited by 198
Patient-Reported Outcome and Observer-Reported Outcome Assessment in Rare Disease Clinical Trials: An ISPOR COA Emerging Good Practices Task Force Report
Benjamin, K. L., Vernon, M., Patrick, D. L., Perfetto, E. M., Nestler-Parr, S., & Burke, L. B. (2017) · Value in Health · doi:10.1016/j.jval.2017.05.015 · Cited by 191
Therapeutic strategies for sickle cell disease: towards a multi-agent approach
Telen, M. J., Malik, P., & Vercellotti, G. M. (2018) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0003-2 · Cited by 188
Rare diseases, orphan drugs and their regulation: questions and misconceptions
Tambuyzer, E. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3275 · Cited by 182
Self-citation
Targeting RNA splicing for disease therapy
Havens, M. A., Duelli, D. M., & Hastings, M. L. (2013) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1158 · Cited by 173
Heterogeneous Network Edge Prediction: A Data Integration Approach to Prioritize Disease-Associated Genes
Himmelstein, D. S., & Baranzini, S. E. (2015) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1004259 · Cited by 172
Pompe Disease: Early Diagnosis and Early Treatment Make a Difference
Chien, Y., Hwu, W., & Lee, N. (2013) · Pediatrics & Neonatology · doi:10.1016/j.pedneo.2013.03.009 · Cited by 171
Prevention of pathology in mdx mice by expression of utrophin: analysis using an inducible transgenic expression system
Squire, S. E. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.26.3333 · Cited by 170
Lipid nanoparticles for targeted siRNA delivery - going from bench to bedside
Zatsepin (2016) · International Journal of Nanomedicine · doi:10.2147/ijn.s106625 · Cited by 162
Pharmacological advances for treatment in Duchenne muscular dystrophy
Guiraud, S., & Davies, K. E. (2017) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2017.04.002 · Cited by 160
Self-citation
Taliglucerase alfa: An enzyme replacement therapy using plant cell expression technology
Grabowski, G. A., Golembo, M., & Shaaltiel, Y. (2014) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2014.02.011 · Cited by 153
Drug screening for human genetic diseases using iPSC models
Elitt, M. S., Barbar, L., & Tesar, P. J. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy186 · Cited by 147
DrugCentral 2018: an update
Ursu, O., Holmes, J., Bologa, C., Yang, J. J., Mathias, S. L., Stathias, V., Nguyễn, Ð.-T., Schürer, S. C., & Oprea, T. I. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky963 · Cited by 145
Self-citation
Home monitoring of patients with cystic fibrosis to identify and treat acute pulmonary exacerbations. eICE study results
Lechtzin, N., Mayer-Hamblett, N., West, N. E., Allgood, S., Wilhelm, E., Khan, U., Aitken, M. L., Ramsey, B. W., Boyle, M. P., Mogayzel, P. J., et al. (2017) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201610-2172oc · Cited by 127
Estimating the clinical cost of drug development for orphan versus non-orphan drugs
Jayasundara, K., Hollis, A., Krahn, M. D., Mamdani, M., Hoch, J. S., & Grootendorst, P. V. (2019) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-018-0990-4 · Cited by 127
Glimmers in illuminating the druggable genome
Rodgers, G., Austin, C., Anderson, J., Pawlyk, A., Colvis, C., Margolis, R., & Baker, J. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.252 · Cited by 126
Self-citation
Treatment strategies for lysosomal storage disorders
Beck, M. (2017) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.13600 · Cited by 114
Advances and innovations in haemophilia treatment
Peters, R., & Harris, T. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.70 · Cited by 114
Associating Drugs, Targets and Clinical Outcomes into an Integrated Network Affords a New Platform for Computer‐Aided Drug Repurposing
Oprea, T. I., Nielsen, S. K., Ursu, O., Yang, J. J., Taboureau, O., Mathias, S. L., Kouskoumvekaki, I. A., Sklar, L. A., & Bologa, C. (2011) · Molecular Informatics · doi:10.1002/minf.201100023 · Cited by 113
Self-citation
Antibody‐drug conjugates: Promising and efficient tools for targeted cancer therapy
Nasiri, H., Valedkarimi, Z., Maleki, L. A., & Majidi, J. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26435 · Cited by 103
Disciplined approach to drug discovery and early development
Plenge, R. M. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf2608 · Cited by 102
Antisense Oligonucleotide-Mediated Exon Skipping for Duchenne Muscular Dystrophy: Progress and Challenges
Arechavala‐Gomeza, V., Anthony, K., Morgan, J. E., & Muntoni, F. (2012) · Current Gene Therapy · doi:10.2174/156652312800840621 · Cited by 94
Designing Human Antibodies by Phage Display
Frenzel, A., Kügler, J., Helmsing, S., Meier, D., Schirrmann, T., Hust, M., & Dübel, S. (2017) · Transfusion Medicine and Hemotherapy · doi:10.1159/000479633 · Cited by 90
Translational Bioinformatics: Past, Present, and Future
Tenenbaum, J. D. (2016) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2016.01.003 · Cited by 86
Overview of the development of Orthoclone OKT3: monoclonal antibody for therapeutic use in transplantation.
Goldstein, G. (1987) · PubMed · Cited by 77
Therapeutic Application of Pluripotent Stem Cells: Challenges and Risks
Martin, U. (2017) · Frontiers in Medicine · doi:10.3389/fmed.2017.00229 · Cited by 77
Adeno-Associated Virus Type 2 and Hepatocellular Carcinoma?
Berns, K. I., Byrne, B. J., Flotte, T. R., Gao, G., Hauswirth, W. W., Herzog, R. W., Muzyczka, N., VandenDriessche, T., Xiao, X., Zolotukhin, S., et al. (2015) · Human Gene Therapy · doi:10.1089/hum.2015.29014.kib · Cited by 75
The global landscape of cancer cell therapy
Tang, J., Hubbard-Lucey, V. M., Pearce, L., O’Donnell-Tormey, J., & Shalabi, A. M. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.74 · Cited by 74
Finding disease-related genomic experiments within an international repository: first steps in translational bioinformatics.
Butte, A. J., & Chen, R. (2006) · PubMed · Cited by 67
Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770
Goor, F. V., Burton, B., Hadidaꝉ, S., Grootenhuis, P. D. J., Olson, E. R., Wine, J. J., Frizzell, R. A., Ashlock, M. A., & Negulescu, P. A. (2009) · Journal of Cystic Fibrosis · doi:10.1016/s1569-1993(09)60072-2 · Cited by 67
How close are we to therapies for Sanfilippo disease?
Gaffke, L., Pierzynowska, K., Piotrowska, E., & Węgrzyn, G. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-0111-4 · Cited by 62
Usefulness of an Implantable Loop Recorder to Detect Clinically Relevant Arrhythmias in Patients With Advanced Fabry Cardiomyopathy
Weidemann, F., Maier, S. K. G., Störk, S., Brunner, T. B., Liu, D., Hu, K., Seydelmann, N., Schneider, A., Becher, J., Canaan‐Kühl, S., et al. (2016) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2016.04.033 · Cited by 61
The Rules of Engagement: CTTI Recommendations for Successful Collaborations Between Sponsors and Patient Groups Around Clinical Trials
Bloom, D. L., Beetsch, J., Harker, M. J., Hesterlee, S. E., Moreira, P., Patrick‐Lake, B., Selig, W. K. D., Sherman, J. W., Smith, S. K., Valentine, J. E., et al. (2017) · Therapeutic Innovation & Regulatory Science · doi:10.1177/2168479017720247 · Cited by 58
Self-citation
Recent advances in developing therapeutics for cystic fibrosis
Strug, L. J., Stephenson, A. L., Panjwani, N., & Harris, A. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy188 · Cited by 56
Development of gene therapy for blood disorders: an update
Nienhuis, A. W. (2013) · Blood · doi:10.1182/blood-2013-04-453209 · Cited by 55
Perspective on Adeno-Associated Virus Capsid Modification for Duchenne Muscular Dystrophy Gene Therapy
Nance, M. E., & Duan, D. (2015) · Human Gene Therapy · doi:10.1089/hum.2015.107 · Cited by 52
Preparing for the Future of Rare Diseases
Groft, S. C., & de la Paz, M. P. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-67144-4_34 · Cited by 48
Self-citation
“NextGen” Biologics: Bispecific Antibodies and Emerging Clinical Results
Thakur, A. B., & Lum, L. G. (2016) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2016.1150996 · Cited by 46
Worldwide collaboration for orphan drug designation
Mariz, S., Reese, J. H., Westermark, K., Greene, L. H., Goto, T., Hoshino, T., Llinares, J., & Sepodes, B. M. N. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.80 · Cited by 45
Heart Regeneration: Opportunities and Challenges for Drug Discovery with Novel Chemical and Therapeutic Methods or Agents
Plowright, A. T., Engkvist, O., Gill, A. L., Knerr, L., & Wang, Q. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201307034 · Cited by 41
Dose-Dependent Lowering of Mutant Huntingtin Using Antisense Oligonucleotides in Huntington Disease Patients
van Roon‐Mom, W., Roos, R. A. C., & de Bot, S. T. (2018) · Nucleic Acid Therapeutics · doi:10.1089/nat.2018.0720 · Cited by 41
Assessing the Efficacy and Safety of an 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017) in the Idiopathic Intracranial Hypertension Drug Trial, IIH:DT: Clinical Methods and Design for a Phase II Randomized Controlled Trial
Markey, K. A., Ottridge, R. S., Mitchell, J., Rick, C., Woolley, R. L., Ives, N. J., Nightingale, P., & Sinclair, A. J. (2017) · JMIR Research Protocols · doi:10.2196/resprot.7806 · Cited by 39
The Case for the Use of Patient and Caregiver Perception of Change Assessments in Rare Disease Clinical Trials: A Methodologic Overview
Contesse, M. G., Valentine, J. E., Wall, T. E., & Leffler, M. G. (2019) · Advances in Therapy · doi:10.1007/s12325-019-00920-x · Cited by 39
Self-citation
Preliminary studies on the palatability of grasses, legumes and herbs to horses
ARCHER, M. (1971) · Veterinary Record · doi:10.1136/vr.89.9.236 · Cited by 36
eRAM: encyclopedia of rare disease annotations for precision medicine
Jia, J., An, Z., Ming, Y., Guo, Y., Li, W., Liang, Y., Guo, D., Li, X., Tai, J., Chen, G., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gkx1062 · Cited by 35
The art and science of choosing efficacy endpoints for rare disease clinical trials
Cox, G. F. (2018) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.38629 · Cited by 35
Innovative approach for self-management and social welfare of children with cystic fibrosis in Europe: development, validation and implementation of an mHealth tool (MyCyFAPP)
Calvo‐Lerma, J., Martinez‐Jimenez, C. P., Ramos, J. P. L., Andrés, A., Crespo‐Escobar, P., Stav, E., Schauber, C., Pannese, L., Hulst, J. M., Suárez, L., et al. (2017) · BMJ Open · doi:10.1136/bmjopen-2016-014931 · Cited by 34
Emerging therapies and therapeutic concepts for lysosomal storage diseases
Kirkegaard, T. (2013) · Expert Opinion on Orphan Drugs · doi:10.1517/21678707.2013.780970 · Cited by 32
How CRISPR is transforming drug discovery
Scott, A. J. (2018) · Nature · doi:10.1038/d41586-018-02477-1 · Cited by 32
Alpha-1 proteinase inhibitors for the treatment of alpha-1 antitrypsin deficiency: safety, tolerability, and patient outcomes
Chotirmall, S. H., Al‐Alawi, M., McEnery, T., & McElvaney, N. G. (2015) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s51474 · Cited by 28
The haemtrack home therapy reporting system: Design, implementation, strengths and weaknesses: A report from UK Haemophilia Centre Doctors Organisation
Hay, C. R. M., Xiang, H., Scott, M. J., Collins, P., Liesner, R. J., Dolan, G., & Hollingsworth, R. (2017) · Haemophilia · doi:10.1111/hae.13287 · Cited by 28
Historical Perspective on the Current Renaissance for Hematopoietic Stem Cell Gene Therapy
Kohn, D. B. (2017) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2017.06.006 · Cited by 28
Gene Therapy for Hemophilia: Progress to Date
Chapin, J. C., & Monahan, P. E. (2017) · BioDrugs · doi:10.1007/s40259-017-0255-0 · Cited by 25
How Surrogate and Chemical Genetics in Model Organisms Can Suggest Therapies for Human Genetic Diseases
Strynatka, K. A., Gurrola-Gal, M. C., Berman, J. N., & McMaster, C. R. (2018) · Genetics · doi:10.1534/genetics.117.300124 · Cited by 25
Amount and intensity of daily living activities in Charcot–Marie–Tooth 1A patients
Menotti, F., Laudani, L., Damiani, A., & Macaluso, A. (2013) · Brain and Behavior · doi:10.1002/brb3.187 · Cited by 24
The importance of natural histories for rare diseases
Gavin, P. (2015) · Expert Opinion on Orphan Drugs · doi:10.1517/21678707.2015.1063415 · Cited by 23
Reengineered AAV Vectors: Old Dog, New Tricks
The University of North Carolina at Chapel Hill University Libraries (2020) · PubMed · doi:10.17615/9jm8-4r29 · Cited by 20
Enzyme Replacement Therapies and Immunogenicity in Lysosomal Storage Diseases: Is There a Pattern?
Harmatz, P. (2015) · Clinical Therapeutics · doi:10.1016/j.clinthera.2015.06.004 · Cited by 19
Digitalisierungsstrategien für das Krankenhaus der Zukunft
Deiters, W., Burmann, A., & Meister, S. (2018) · Der Urologe · doi:10.1007/s00120-018-0731-2 · Cited by 19
Enzyme replacement therapy: lessons learned and emerging questions
Jurecka, A., & Tylki‐Szymańska, A. (2015) · Expert Opinion on Orphan Drugs · doi:10.1517/21678707.2015.1017469 · Cited by 18
The Early History of Plasma Cell Tumors in Mice, 1954–1976†
Potter, M. (2007) · Advances in cancer research · doi:10.1016/s0065-230x(06)98002-6 · Cited by 17
Expanding rare disease drug trials based on shared molecular etiology
Brooks, P. J., Tagle, D. A., & Groft, S. (2014) · Nature Biotechnology · doi:10.1038/nbt.2924 · Cited by 17
Self-citation
Induced Pluripotent Stem Cell Therapies for Degenerative Disease of the Outer Retina: Disease Modeling and Cell Replacement
Foggia, V. D., Makwana, P., Ali, R. R., & Sowden, J. C. (2016) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2015.0143 · Cited by 15
Machine Learning to Improve Energy Expenditure Estimation in Children With Disabilities: A Pilot Study in Duchenne Muscular Dystrophy
Pande, A., Mohapatra, P., Nicorici, A., & Han, J. J. (2016) · JMIR Rehabilitation and Assistive Technologies · doi:10.2196/rehab.4340 · Cited by 15
Gene Therapy for Lysosomal Storage Disorders
Gonzalez, E. A., & Baldo, G. (2017) · Journal of Inborn Errors of Metabolism and Screening · doi:10.1177/2326409816689786 · Cited by 12
AAV Vectorization of DSB-mediated Gene Editing Technologies
Moser, R. J., & Hirsch, M. L. (2016) · Current Gene Therapy · doi:10.2174/1566523216666160602213738 · Cited by 11
The NIH-Industry New Therapeutic Uses Pilot Program: Demonstrating the Power of Crowdsourcing
Colvis, C. M., & Austin, C. P. (2015) · Assay and Drug Development Technologies · doi:10.1089/adt.2015.29006.cmcdrrr · Cited by 7
Self-citation
Alglucosidase alfa: first available treatment for Pompe disease
Nicolino, M. P. (2007) · Therapy · doi:10.2217/14750708.4.3.271 · Cited by 5
A higher dose of enzyme therapy in patients with classic infantile Pompe disease seems to improve ventilator-free survival and motor function
van Gelder, C., Plug, I., Kroos, M. A., Reuser, A. J. J., & van der Ploeg, A. (2013) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-14-s2-p19 · Cited by 5
FDA approves first drug for Duchenne muscular dystrophy
Blank, C. (2016) · Formulary ENews · Cited by 5
MICROBIAL COMMUNITY COMPOSITION IN EXPLANTED CYSTIC FIBROSIS (CF) LUNGS
Tunney, M. M., McLean, D., Einarsson, G. G., Elborn, J. S., Lammertyn, E. J., Bosch, B., Vermeulen, F. L., Verleden, S. E., Boeck, K. D., Dupont, L., et al. (2015) · Research Portal (Queen's University Belfast) · doi:10.1002/ppul.23295

Research works printed but not linked: 5

LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Enzyme Replacement Therapy. National Institute of Diabetes and Digestive and Kidney Diseases https://www.ncbi.nlm.nih.gov/books/NBK548796/ (2016).
Field, M. J. & Boat, T. F. (eds) Rare Diseases and Orphan Products (National Academies Press, 2010).
Journal of Gene Medicine. Gene therapy clinical trials worldwide. Wiley http://www.abedia.com/wiley/vectors.php (2018).
Kaiser, J. New gene-editing treatment might help treat a rare disorder, hints first human test. Science https://doi.org/10.1126/science.aav3226 (2018). · DOI
Alliance for Regenerative Medicine. Quarterly data report Q3. ARM http://alliancerm.org/wp-content/uploads/2018/10/ARM_Q3_2018_Web-1.pdf (2018).

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Zhang, Z., Zhou, L., Xie, N., Nice, E. C., Zhang, T., Cui, Y., & Huang, C. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00213-8 · Cited by 544
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Authors: Tambuyzer, E., Vandendriessche, B., Austin, C. P., Brooks, P. J., Larsson, K., Miller Needleman, K. I., Valentine, J., Davies, K., Groft, S. C., Preti, R., Oprea, T. I., & Prunotto, M.
Affiliations: Rare Disease Foundation (CA)
Case Western Reserve University (US)
National Institutes of Health (US)
European Medicines Agency (NL)
University of Oxford (GB)
University of New Mexico (US)
University of Geneva (CH)
Corresponding author: Tambuyzer, Erik
Prunotto, Marco
ORCID: Vandendriessche, Benjamin
Austin, Christopher P.
Brooks, Philip J.
Larsson, Kristina
Valentine, James
Davies, Kay
Groft, Stephen C.
Oprea, Tudor I.
Prunotto, Marco
Venue: Nature Reviews Drug Discovery
Publisher: Springer Science and Business Media LLC
Published: 2019-12-13
Volume: 19
Issue: 2
Pages: 93-111
ISSN: 1474-1776 (ISSN-L)
1474-1784
DOI: 10.1038/s41573-019-0049-9
OpenAlex: W2994844251
Semantic Scholar: b81783b225e115f42fe2a6eee47b0a650e5dfc28
Cited by: 357
References: 166
Citations by year: 2026: 44 · 2025: 52 · 2024: 70 · 2023: 68 · 2022: 58 · 2021: 43 · 2020: 21 · 2019: 1
FWCI: 8.52
Type: journal article
Language: en
Update notices: correction (2020-01-08)
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Reviews Drug Discovery (publishedVersion)
PubMed (publishedVersion)
Topics: Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Keywords: rare diseases, orphan drugs, therapeutic modalities, small molecules, monoclonal antibodies, protein replacement therapy, oligonucleotides, gene therapy, cell therapy, drug repurposing, drug development, regulatory pathways, patient engagement, digital tools, translational gap
MeSH terms: Drug Development, Humans, Orphan Drug Production, Drug Approval, Rare Diseases, Drug Repositioning

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Therapies for rare diseases: therapeutic modalities, progress and challenges ahead

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