Next Generation Therapies: Innovative Drug Development Approaches for Rare Diseases

Scientific Reference List

  1. Globalgenes.org. https://globalgenes.org/rare-diseases-facts-statistics/
  2. Konermann S, Lotfy P, Brideau NJ, Oki J, Shokhirev MN, Hsu PD. Transcriptome engineering with rna-targeting type vi-d crispr effectors. Cell. 2018;173:665-676 e614
  3. Gagne JJ, Thompson L, O'Keefe K, Kesselheim AS. Innovative research methods for studying treatments for rare diseases: Methodological review. BMJ. 2014;349:g6802
  4. Boycott KM, Vanstone MR, Bulman DE, MacKenzie AE. Rare-disease genetics in the era of next-generation sequencing: Discovery to translation. Nature reviews. Genetics. 2013;14:681-691
  5. Attwood MM, Rask-Andersen M, Schioth HB. Orphan drugs and their impact on pharmaceutical development. Trends Pharmacol Sci. 2018;39:525-535
  6. Dunbar CE, High KA, Joung JK, Kohn DB, Ozawa K, Sadelain M. Gene therapy comes of age. Science. 2018;359
  7. Kotterman MA, Chalberg TW, Schaffer DV. Viral vectors for gene therapy: Translational and clinical outlook. Annu Rev Biomed Eng. 2015;17:63-89
  8. Schuster DJ, Dykstra JA, Riedl MS, Kitto KF, Belur LR, McIvor RS, Elde RP, Fairbanks CA, Vulchanova Biodistribution of adeno-associated virus serotype 9 (AAV9) vector after intrathecal and intravenous delivery in mouse. Front Neuroanat. 2014; 8:42
  9. Finer M, Glorioso J. A brief account of viral vectors and their promise for gene therapy. Gene therapy. 2017;24:1-2
  10. Colella P, Ronzitti G, Mingozzi F. Emerging issues in aav-mediated in vivo gene therapy. Molecular therapy. Methods & clinical development. 2018;8:87-104
  11. Joshi CR, Labhasetwar V, Ghorpade A. Destination brain: The past, present, and future of therapeutic gene delivery. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology. 2017;12:51-83
  12. Lykken EA, Shyng C, Edwards RJ, Rozenberg A, Gray SJ. Recent progress and considerations for aav gene therapies targeting the central nervous system. Journal of neurodevelopmental disorders. 2018;10:16
  13. Merkel SF, Andrews AM, Lutton EM, Mu D, Hudry E, Hyman BT, et al. Trafficking of adeno-associated virus vectors across a model of the blood-brain barrier; a comparative study of transcytosis and transduction using primary human brain endothelial cells. Journal of neurochemistry. 2017;140:216-230
  14. Blaese RM, Culver KW, Miller AD, Carter CS, Fleisher T, Clerici M, et al. T lymphocyte-directed gene therapy for ada- scid: Initial trial results after 4 years. Science. 1995;270:475-480
  15. Chira S, Jackson CS, Oprea I, Ozturk F, Pepper MS, Diaconu I, et al. Progresses towards safe and efficient gene therapy vectors. Oncotarget. 2015;6:30675-30703
  16. Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. The New England journal of medicine. 2017;377:1713-1722
  17. Rangarajan S, Walsh L, Lester W, Perry D, Madan B, Laffan M, et al. Aav5-factor viii gene transfer in severe hemophilia a. The New England journal of medicine. 2017;377:2519-2530
  18. George LA, Sullivan SK, Giermasz A, Rasko JEJ, Samelson-Jones BJ, Ducore J, et al. Hemophilia b gene therapy with a high-specific-activity factor ix variant. The New England journal of medicine. 2017;377:2215-2227
  19. Singh NN, Howell MD, Androphy EJ, Singh RN. How the discovery of iss-n1 led to the first medical therapy for spinal muscular atrophy. Gene therapy. 2017;24:520-526
  20. Ginn SL, Amaya AK, Alexander IE, Edelstein M, Abedi MR. Gene therapy clinical trials worldwide to 2017: An update. The journal of gene medicine. 2018;20:e3015
  21. Franchini M, Mannucci PM. Past, present and future of hemophilia: A narrative review. Orphanet journal of rare diseases. 2012;7:24
  22. Balkaransingh P, Young G. Novel therapies and current clinical progress in hemophilia a. Therapeutic advances in hematology. 2018;9:49-61
  23. Maeder ML, Gersbach CA. Genome-editing technologies for gene and cell therapy. Molecular therapy : the journal of the American Society of Gene Therapy. 2016;24:430-446
  24. Schneller JL, Lee CM, Bao G, Venditti CP. Genome editing for inborn errors of metabolism: Advancing towards the clinic. BMC medicine. 2017;15:43
  25. Alzforum.org https://www.alzforum.org/news/research-news/antisense-therapy-cuts-huntingtin-protein-csf-half.
  26. Cornu TI, Mussolino C, Cathomen T. Refining strategies to translate genome editing to the clinic. Nature medicine. 2017;23:415-423
  27. Li H, Haurigot V, Doyon Y, Li T, Wong SY, Bhagwat AS, et al. In vivo genome editing restores haemostasis in a mouse model of haemophilia. Nature. 2011;475:217-221
  28. Zinn E, Pacouret S, Khaychuk V, Turunen HT, Carvalho LS, Andres-Mateos E, et al. In silico reconstruction of the viral evolutionary lineage yields a potent gene therapy vector. Cell Rep. 2015;12:1056-1068
  29. Burnight ER, Wiley LA, Mullins RF, Stone EM, Tucker BA. Gene therapy using stem cells. Cold Spring Harb Perspect Med. 2014;5
  30. Anderson RH, Francis KR. Modeling rare diseases with induced pluripotent stem cell technology. Mol Cell Probes. 2018;40:52-59
  31. Hirsch T, Rothoeft T, Teig N, Bauer JW, Pellegrini G, De Rosa L, et al. Regeneration of the entire human epidermis using transgenic stem cells. Nature. 2017;551:327-332
  32. Beaudet AL, Meng L. Gene-targeting pharmaceuticals for single-gene disorders. Hum Mol Genet. 2016;25:R18-26
  33. Wild EJ, Tabrizi SJ. Therapies targeting DNA and rna in huntington's disease. Lancet Neurol. 2017;16:837-847
  34. Crooke ST, Witztum JL, Bennett CF, Baker BF. Rna-targeted therapeutics. Cell metabolism. 2018;27:714-739
  35. Gallego-Paez LM, Bordone MC, Leote AC, Saraiva-Agostinho N, Ascensao-Ferreira M, Barbosa-Morais NL. Alternative splicing: The pledge, the turn, and the prestige : The key role of alternative splicing in human biological systems. Human genetics. 2017;136:1015-1042
  36. Chabot B, Shkreta L. Defective control of pre-messenger rna splicing in human disease. The Journal of cell biology. 2016;212:13-27
  37. Scotti MM, Swanson MS. Rna mis-splicing in disease. Nature reviews. Genetics. 2016;17:19-32
  38. Sune-Pou M, Prieto-Sanchez S, Boyero-Corral S, Moreno-Castro C, El Yousfi Y, Sune-Negre JM, et al. Targeting splicing in the treatment of human disease. Genes. 2017;8
  39. Cooper TA, Wan L, Dreyfuss, G. RNA and disease. Cell. 2009; 13694); 777-93.
  40. Parente V, Corti S. Advances in spinal muscular atrophy therapeutics. Therapeutic advances in neurological disorders. 2018;11:1756285618754501
  41. Staropoli JF, Li H, Chun SJ, Allaire N, Cullen P, Thai A, et al. Rescue of gene-expression changes in an induced mouse model of spinal muscular atrophy by an antisense oligonucleotide that promotes inclusion of smn2 exon 7. Genomics. 2015;105:220-228
  42. Mercuri E, Darras BT, Chiriboga CA, Day JW, Campbell C, Connolly AM, et al. Nusinersen versus sham control in later-onset spinal muscular atrophy. The New England journal of medicine. 2018;378:625-635
  43. Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. The New England journal of medicine. 2017;377:1723-1732
  44. Dowling JJ, H DG, Cohn RD, Campbell C. Treating pediatric neuromuscular disorders: The future is now. American journal of medical genetics. Part A. 2018;176:804-841
  45. Aoki Y, Nakamura A, Yokota T, Saito T, Okazawa H, Nagata T, et al. In-frame dystrophin following exon 51-skipping improves muscle pathology and function in the exon 52-deficient mdx mouse. Molecular therapy : the journal of the American Society of Gene Therapy. 2010;18:1995-2005
  46. Robinson-Hamm JN, Gersbach CA. Gene therapies that restore dystrophin expression for the treatment of duchenne muscular dystrophy. Human genetics. 2016;135:1029-1040
  47. Maruyama R, Echigoya Y, Caluseriu O, Aoki Y, Takeda S, Yokota T. Systemic delivery of morpholinos to skip multiple exons in a dog model of duchenne muscular dystrophy. Methods Mol Biol. 2017;1565:201-213
  48. Lim KR, Maruyama R, Yokota T. Eteplirsen in the treatment of duchenne muscular dystrophy. Drug design, development and therapy. 2017;11:533-545
  49. Mendell JR, Goemans N, Lowes LP, Alfano LN, Berry K, Shao J, et al. Longitudinal effect of eteplirsen versus historical control on ambulation in duchenne muscular dystrophy. Ann Neurol. 2016;79:257-271
  50. Stein CA, Castanotto D. Fda-approved oligonucleotide therapies in 2017. Molecular therapy : the journal of the American Society of Gene Therapy. 2017;25:1069-1075
  51. Ajufo E, Rader DJ. New therapeutic approaches for familial hypercholesterolemia. Annu Rev Med. 2018;69:113-131
  52. Shen X, Corey DR. Chemistry, mechanism and clinical status of antisense oligonucleotides and duplex rnas. Nucleic Acids Res. 2018;46:1584-1600
  53. Kaczmarek JC, Kowalski PS, Anderson DG. Advances in the delivery of rna therapeutics: From concept to clinical reality. Genome medicine. 2017;9:60
  54. Rupaimoole R, Slack FJ. Microrna therapeutics: Towards a new era for the management of cancer and other diseases. Nature reviews. Drug discovery. 2017;16:203-222
  55. Vogel P, Moschref M, Li Q, Merkle T, Selvasaravanan KD, Li JB, et al. Efficient and precise editing of endogenous transcripts with snap-tagged adars. Nat Methods. 2018;15:535-538
  56. Cox DBT, Gootenberg JS, Abudayyeh OO, Franklin B, Kellner MJ, Joung J, et al. Rna editing with crispr-cas13. Science. 2017;358:1019-1027
  57. Zamecnik PC, Raychowdhury MK, Tabatadze DR, Cantiello HF. Reversal of cystic fibrosis phenotype in a cultured delta508 cystic fibrosis transmembrane conductance regulator cell line by oligonucleotide insertion. Proceedings of the National Academy of Sciences of the United States of America. 2004;101:8150-8155
  58. Quon BS, Rowe SM. New and emerging targeted therapies for cystic fibrosis. BMJ. 2016;352:i859
  59. Wang DW, Mokhonova EI, Kendall GC, Becerra D, Naeini YB, Cantor RM, et al. Repurposing dantrolene for long-term combination therapy to potentiate antisense-mediated dmd exon skipping in the mdx mouse. Mol Ther Nucleic Acids. 2018;11:180-191
  60. Sun W, Zheng W, Simeonov A. Drug discovery and development for rare genetic disorders. American journal of medical genetics. Part A. 2017;173:2307-2322
  61. Whyte MP. Hypophosphatasia: An overview for 2017. Bone. 2017;102:15-25
  62. Yari M, Ghoshoon MB, Vakili B, Ghasemi Y. Therapeutic enzymes: Applications and approaches to pharmacological improvement. Current pharmaceutical biotechnology. 2017;18:531-540
  63. Whyte MP. Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment. Nature reviews. Endocrinology. 2016;12:233-246
  64. Millan JL, Narisawa S, Lemire I, Loisel TP, Boileau G, Leonard P, et al. Enzyme replacement therapy for murine hypophosphatasia. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2008;23:777-787
  65. Whyte MP, Greenberg CR, Salman NJ, Bober MB, McAlister WH, Wenkert D, et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. The New England journal of medicine. 2012;366:904-913
  66. Sweeney P, Park H, Baumann M, Dunlop J, Frydman J, Kopito R, et al. Protein misfolding in neurodegenerative diseases: Implications and strategies. Translational neurodegeneration. 2017;6:6
  67. Valastyan JS, Lindquist S. Mechanisms of protein-folding diseases at a glance. Disease models & mechanisms. 2014;7:9-14
  68. Dubnikov T, Ben-Gedalya T, Cohen E. Protein quality control in health and disease. Cold Spring Harbor perspectives in biology. 2017;9
  69. Mohamed FE, Al-Gazali L, Al-Jasmi F, Ali BR. Pharmaceutical chaperones and proteostasis regulators in the therapy of lysosomal storage disorders: Current perspective and future promises. Frontiers in pharmacology. 2017;8:448
  70. Tao YX, Conn PM. Pharmacoperones as novel therapeutics for diverse protein conformational diseases. Physiological reviews. 2018;98:697-725
  71. Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR, et al. Treatment of fabry's disease with the pharmacologic chaperone migalastat. The New England journal of medicine. 2016;375:545-555
  72. Adams D, Cauquil C, Labeyrie C, Beaudonnet G, Algalarrondo V, Theaudin M. Ttr kinetic stabilizers and ttr gene silencing: A new era in therapy for familial amyloidotic polyneuropathies. Expert opinion on pharmacotherapy. 2016;17:791-802
  73. Capper MJ, Wright GSA, Barbieri L, Luchinat E, Mercatelli E, McAlary L, et al. The cysteine-reactive small molecule ebselen facilitates effective sod1 maturation. Nature communications. 2018;9:1693
  74. Sievers SA, Karanicolas J, Chang HW, Zhao A, Jiang L, Zirafi O, et al. Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation. Nature. 2011;475:96-100
  75. Seidler PM, Boyer DR, Rodriguez JA, Sawaya MR, Cascio D, Murray K, et al. Structure-based inhibitors of tau aggregation. Nature chemistry. 2018;10:170-176
  76. Singh S, Kumar N, Dwiwedi P, Charan J, Kaur R, Sidhu P, et al. Monoclonal antibodies: A review. Curr Clin Pharmacol. 2017
  77. Carter PJ, Lazar GA. Next generation antibody drugs: Pursuit of the 'high-hanging fruit'. Nature reviews. Drug discovery. 2018;17:197-223
  78. Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, et al. Factor viii-mimetic function of humanized bispecific antibody in hemophilia a. The New England journal of medicine. 2016;374:2044-2053
  79. Hung SY, Fu WM. Drug candidates in clinical trials for alzheimer's disease. J Biomed Sci. 2017;24:47
  80. Bittar A, Sengupta U, Kayed R. Prospects for strain-specific immunotherapy in alzheimer's disease and tauopathies. NPJ Vaccines. 2018;3:9
  81. Cutting GR. Cystic fibrosis genetics: From molecular understanding to clinical application. Nature reviews. Genetics. 2015;16:45-56
  82. Okiyoneda T, Veit G, Dekkers JF, Bagdany M, Soya N, Xu H, et al. Mechanism-based corrector combination restores deltaf508-cftr folding and function. Nat Chem Biol. 2013;9:444-454
  83. Mijnders M, Kleizen B, Braakman I. Correcting cftr folding defects by small-molecule correctors to cure cystic fibrosis. Current opinion in pharmacology. 2017;34:83-90
  84. Accurso FJ, Rowe SM, Clancy JP, Boyle MP, Dunitz JM, Durie PR, et al. Effect of vx-770 in persons with cystic fibrosis and the g551d-cftr mutation. The New England journal of medicine. 2010;363:1991-2003
  85. Van Goor F, Hadida S, Grootenhuis PD, Burton B, Stack JH, Straley KS, et al. Correction of the f508del-cftr protein processing defect in vitro by the investigational drug vx-809. Proceedings of the National Academy of Sciences of the United States of America. 2011;108:18843-18848
  86. Van Goor F, Hadida S, Grootenhuis PD, Burton B, Cao D, Neuberger T, et al. Rescue of cf airway epithelial cell function in vitro by a cftr potentiator, vx-770. Proceedings of the National Academy of Sciences of the United States of America. 2009;106:18825-18830
  87. Kym PR, Wang X, Pizzonero M, Van der Plas SE. Recent progress in the discovery and development of small-molecule modulators of cftr. Prog Med Chem. 2018;57:235-276
  88. Hanrahan JW, Matthes E, Carlile G, Thomas DY. Corrector combination therapies for f508del-cftr. Current opinion in pharmacology. 2017;34:105-111
  89. Carlile GW, Yang Q, Matthes E, Liao J, Radinovic S, Miyamoto C, et al. A novel triple combination of pharmacological chaperones improves f508del-cftr correction. Sci Rep. 2018;8:11404
  90. Maiuri L, Raia V, Kroemer G. Strategies for the etiological therapy of cystic fibrosis. Cell Death Differ. 2017;24:1825-1844
  91. Rinaldi C, Mager I, Wood MJ. Proteostasis and diseases of the motor unit. Front Mol Neurosci. 2016;9:164
  92. Kalmar B, Greensmith L. Cellular chaperones as therapeutic targets in als to restore protein homeostasis and improve cellular function. Front Mol Neurosci. 2017;10:251
  93. Walters HE, Cox LS. Mtorc inhibitors as broad-spectrum therapeutics for age-related diseases. Int J Mol Sci. 2018;19
  94. Franz DN, Capal JK. Mtor inhibitors in the pharmacologic management of tuberous sclerosis complex and their potential role in other rare neurodevelopmental disorders. Orphanet journal of rare diseases. 2017;12:51
  95. Matsui M, Corey DR. Non-coding rnas as drug targets. Nature reviews. Drug discovery. 2017;16:167-179
  96. Ransohoff JD, Wei Y, Khavari PA. The functions and unique features of long intergenic non-coding rna. Nat Rev Mol Cell Biol. 2018;19:143-157
  97. Salvatore M, Magrelli A, Taruscio D. The role of micrornas in the biology of rare diseases. Int J Mol Sci. 2011;12:6733-6742
  98. Chakraborty C, Sharma AR, Sharma G, Doss CGP, Lee SS. Therapeutic mirna and sirna: Moving from bench to clinic as next generation medicine. Mol Ther Nucleic Acids. 2017;8:132-143
  99. Gomez IG, MacKenna DA, Johnson BG, Kaimal V, Roach AM, Ren S, et al. Anti-microrna-21 oligonucleotides prevent alport nephropathy progression by stimulating metabolic pathways. J Clin Invest. 2015;125:141-156
  100. Long Y, Wang X, Youmans DT, Cech TR. How do lncrnas regulate transcription? Sci Adv. 2017;3:eaao2110
  101. Prachayasittikul V, Prathipati P, Pratiwi R, Phanus-Umporn C, Malik AA, Schaduangrat N, et al. Exploring the epigenetic drug discovery landscape. Expert Opin Drug Discov. 2017;12:345-362
  102. Delgado-Morales R, Agis-Balboa RC, Esteller M, Berdasco M. Epigenetic mechanisms during ageing and neurogenesis as novel therapeutic avenues in human brain disorders. Clin Epigenetics. 2017;9:67
  103. Bjornsson HT. The mendelian disorders of the epigenetic machinery. Genome Res. 2015;25:1473-1481
  104. Jia H, Morris CD, Williams RM, Loring JF, Thomas EA. Hdac inhibition imparts beneficial transgenerational effects in huntington's disease mice via altered DNA and histone methylation. Proceedings of the National Academy of Sciences of the United States of America. 2015;112:E56-64
  105. Kim Y, Lee HM, Xiong Y, Sciaky N, Hulbert SW, Cao X, et al. Targeting the histone methyltransferase g9a activates imprinted genes and improves survival of a mouse model of prader-willi syndrome. Nature medicine. 2017;23:213-222
  106. Korb E, Herre M, Zucker-Scharff I, Gresack J, Allis CD, Darnell RB. Excess translation of epigenetic regulators contributes to fragile x syndrome and is alleviated by brd4 inhibition. Cell. 2017;170:1209-1223 e1220
  107. Zamvil SS, Spencer CM, Baranzini SE, Cree BAC. The gut microbiome in neuromyelitis optica. Neurotherapeutics. 2018;15:92-101
  108. Kim S, Kim H, Yim YS, Ha S, Atarashi K, Tan TG, et al. Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring. Nature. 2017;549:528-532
  109. Tang AT, Choi JP, Kotzin JJ, Yang Y, Hong CC, Hobson N, et al. Endothelial tlr4 and the microbiome drive cerebral cavernous malformations. Nature. 2017;545:305-310
  110. Clinicaltrials.gov. https://clinicaltrials.gov/ProvidedDocs/02/NCT03335202/Prot_000.pdf