References
  1. Leebeck F and Miesbach W. Gene therapy for hemophilia: a review on clinical benefit, limitations, and remaining issues. Blood 2021; 138(11):923-931.
  2. Nathwani A. Gene therapy for hemophilia. Hematology 2022 ; ASH Education Program: 569-578.
  3. Hover L. Hemophilia A. N Engl J Med 1994; 330(1): 38-47.
  4. Mannucci P and Tuddenham E. The Hemophilias – From Royal Genes to Gene Therapy. N Engl J Med 2001; 344(23): 1773-1779.
  5. Anson D, Hock R, Austen D, Smith K, Brownlee G, Verma I, Miller D. Towards Gene Therapy for Hemophilia B. Mol Biol Med 1987; 4: 11-20.
  6. Manco-Johnson M, Abshire T, Shapiro A, Riske B, Hacker M, Kilcoyne R et al. Prophylaxis versus Episodic Treatment to Prevent Joint Disease in Boys with Severe Hemophilia. N Engl J Med 2007; 357(6): 535-544.
  7. Di Michele D. Immune tolerance induction in haemophilia: evidence and the way forward. J Thromb Haemost 2011; 9(Suppl. 1): 216-225.
  8. Ljung R. The risk associated with indwelling catheters in children with haemophilia. Br J Haematol 2007; 138: 580-586.
  9. Santagostino E, Martinowitz U, Lissitchkov T, Pan-Petesch P, Hanabusa H, Oldenburg J et al. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial. Blood 2016; 127(14): 1761-1769.
  10. Mahlangu J, Powell J, Ragni M, Chowdary P, Josephson N, Pabinger I et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood 2014; 123(3): 317-325.
  11. Von Drygalski A, Chowdary P, Kulkarni R, Susen S, Konkle B, Oldenburg J et al. Efanesoctocog Alfa prophylaxis for patients with severe hemophilia A. N Engl J Med 2023; 388: 310-318
  12. Mahlangu J, Oldenburg J, Paz-Priel, Negrier C, Niggli H, Mancuso M et al. Emicizumab Prophylaxis in Patients Who Have Hemophilia without Inhibitors. N Engl J Med 2018; 379 (9): 811-822.
  13. Young G, Liesner R, Chang T, Sidonio R, Oldenburg J Jimenez-Yuste V et al. A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors. Blood 2019; 134(24): 2127-2138.
  14. Nogami K and Shima M. Current and future therapies for haemophilia – Beyond factor replacement therapies. Br J Haematol 2023; 200:23-34.
  15. Hassan S, Monahan R, Mauser-Bunschoten E, van Vulpen L, Eikenboom J Beckers E et al. Mortality, life expectancy, and cause of death of persons with hemophilia in the Netherlands 2001-2018. J Thromb Haemost 2021; 19: 645-653.
  16. Frei-Jones M, Cepo K, d’Oiron R, Sim Goh A, Mathias M, Odgaard-Jensen J. Subcutaneous Concizumab Prophylaxis in Patients with Hemophilia A or B with Inhibitors: Efficacy and Safety Results by Hemophilia Subtype from Phase 3 Explorer 7 Trial. Blood 2022; 140 (Suppl 1): 466-468.
  17. Young G, Srivastava A, Kavakli K, Ross C, Sathar J, Tran H et al. Efficacy and Safety of Fitusiran Prophylaxis, a siRNA Therapeutic, in a Multicenter Phase 3 Study (ATLAS-INH) in People with Hemophilia A or B, with Inhibitors (PwHI). Blood 2021; 138 (Suppl 1): 4.
  18. Mahhitt L, Dagan R, Yuan Y, Baca Cots M, Bosheva M, Nadhi S et al. Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants. N Engl J Med 2022; 386(9): 837-846.
  19. Dover S, Blanchette V, Wrathall D, Pullenayegum E, Kazandjian D, Song B et al. Hemophilia prophylaxis adherence and bleeding using a tailored, frequency-escalated approach: The Canadian Hemophilia Primary Prophylaxis Study. Res Pract Thromb Haemost 2020 ; 4:318-325.
  20. National Hemophilia Foundation. Stimate Recall Update. [cited 2022 DEC 22] from: https://www.hemophilia.org/news/stimate-recall-update
  21. Abbattista M, Ciavarella A, Noone D, Peyvandi F. Hemorrhagic and thrombotic adverse events associated with Emicizumab and extended half-life factor VIII replacement drugs: EudraVigilance data of 2021.J Thromb Haemost 2023; 21: 5460552.
  22. Bolous N, Chen Y, Wang H, Davidoff A, Devidas M, Jacobs T et al. The cost-effectiveness of gene therapy for severe hemophilia B: a microsimulation study from the United States perspective. Blood2021; 138(18) 1677-1690.
  23. Thornburg C. Prepare the Way for Hemophilia A Gene Therapy. N Engl J Med 2022; 386(11): 1081-1082.
  24. Mahlangu J, Kaczmarek R, von Drygalski A, Shapriro S, Chou C, Ozelo M et al. Two-Year Outcomes of Valoctocogene Roxaparvovec therapy for hemophilia A. N Engl J Med 2023; 388: 694-705.
  25. Pipe S, Leebek F, Recht M, Key N, Castaman G Miesbach S et al. Gene therapy with Etranacogene Dezaparvovec for hemophilia B. N Engl J Med 2023; 388: 706-718.
  26. Pierce G and Herzog R. Two gene therapies for hemophilia available: Now What? Mol Ther 2023; 31: 919-920.
  27. Shah J, Kim H, Sivamurthy K, Monahan P, Fries H. Comprehensive analysis and prediction of long-term durability of factor IX activity following etranacogene dezaparvovec gene therapy in the treatment of hemophilia B.Current Med Research and Opinion 2022
  28. Samelson-Jones B and George L. Adeno-associated virus gene therapy for hemophilia. Annu Rev Med 2023; 74:16.1-16.7.
  29. Carter B. Adeno-associated virus and the development of adeno-associated virus vectors: a historical perspective. Mol Ther  2004; 10, 981–989.
  30. Nault J, Datta S, Imbeaud S, Franconi A, Mallet M, Couchy G et al. Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas. Nat Genet 2015; 47(10): 1187-1195.
  31. Russell D and Grompe M. Adeno-associated virus finds its disease.Nat Genet 2015; 47(10): 1104-1105.
  32. Buening H and Schmidt M. Adeno-associated Vector Toxicity-To Be or Not to Be? Mol Ther 2015 23(11): 1673-1675.
  33. Dave U and Cornetta K. AAV Joins the Rank of Genotoxic Vectors.Mol Ther 2021; 29(2): 418-419.
  34. Chandler R, Sands M, and Venditti C. Recombinant Adeno-Associated Viral Integration and Genotoxicity: Insights from Animal Models.Hum Gene Ther 2017; 28(4): 314-322.
  35. Monahan P, Negrier C, Tarantino M, Valentino L, Mingozzi F. Emerging Immunogenicity and Genotoxicity of Adeno-Associated Virus Vector Gene Therapy for Hemophilia. J Clin Med 2021; 10: 2471
  36. Dalwadi D, Torrens L. Abril-Fornaguera J, Pinyol R, Willoughby C, Posey J et al. Liver Injury Increases the Incidence of HCC following AAV Gene Therapy in Mice. Mol Ther 2021; 29(2): 680-690.
  37. Nguyen G, Everett J, Kafle S, Roche A, Raymond H, Leiby J et al. A long-term study of AAV gene therapy in dogs with hemophilia A identifies clonal expansions of transduced liver cells. Nat Biotechnol 2021; 39: 47-55.
  38. Batty P, Mo A, Hurlbut D, Ishida B, Yates B, Brown C et al. Long-term follow-up of liver-directed, adeno-associated vector-mediated gene therapy in the canine model of hemophilia A. Blood 2022; 140(25): 2673-2683.
  39. Sabatino D, Bushman F, Chandler R, Crystal R, Davidson B, Dolmetsch R et al. Evaluating the state of the science for adeno-associated virus integration: An integrated perspective. Mol Ther 2022; 30(8): 2646-2663.
  40. Niemeyer G, Herzog R, Mount J, Arruda V, Tillson D, Hathcock J et al. Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy. Blood2009; 133(4): 797-806.
  41. Fong S, Yates B, Sihn C, Mattis A, Mitchell N, Liu S et al. Interindividual variability in transgene mRNA and protein production following adeno-associated virus gene therapy for hemophilia A.Nat Medicine 2022; 28: 789-797.
  42. Dalwadi D, Calabria A, Tiyaboonchai A, Posey J, Naugler W, Montini E et al. AAV integration in human hepatocytes. Mol Ther 2021; 29(10): 2898-2909.
  43. Konkle B, Walsh C, Escobar M, Josephson N, Young G, von Drygalski A et al. BAX 335 hemophilia B gene therapy clinical trial results: potential impact of CpG sequences on gene expression. Blood2021; 137(6): 763-774.
  44. National Hemophilia Foundation. Biomarin announced an additional serious adverse event in its gene therapy clinical trial for haemophiia A. [cited 2022 DEC 22] from: https://www.hemophilia.org/sites/default/files/document/files/2022_09_12_Joint-Statement-on-BioMarin-SAE-in-GT%20Trial_FINAL.pdf.
  45. Gorder L, Doshi B, Willis E, Lanza M, Arruda V, Callan M et al. Vector Analysis of Multicentric Lymphoma in a Severe Hemophilia A Dog after AAV Gene Therapy. Blood 2022; 140(Suppl 1): 4919-4920.
  46. Fahs S, Hille M, Shi Q, Weiler H, Montgomery R. A conditional knockout mouse model reveals endothelial cells as the principal and possible exclusive source of plasma factor VIII. Blood 2014; 123(24): 3706-3713.
  47. Poothong J, Pottekat A, Siirin M, Campos A, Paton A, Paton J et al. Factor VIII exhibits chaperone-dependent and glucose-regulated reversible amyloid formation in the endoplasmic reticulum. Blood 2020;135(21): 1899-1911.
  48. Lange A, Altynova E, Nguyen G, Sabatino D. Overexpression of factor VIII after AAV delivery is transiently associated with cellular stress in hemophilia A mice. Mol Ther 2016; 3: 16064.
  49. Butterfield J, Yamada K, Bertolini T, Syed F, Kumar S, Li X et al. Il-15 blockade, and rapamycin rescue multifactorial loss of factor VIII from AAV-transduced hepatocytes in hemophilia A mice. Mol Ther 30; 12: 3552-3569.
  50. Kapelanski-Lamoureaux A, Chen Z, Gao Z, Deng R, Lasaris A, Lebeaupin C et al. Ectopic expression and misfolding in hepatocytes as a cause for hepatocellular carcinoma. Mol Ther 2022; 30: 3524-3551.
  51. Mendell J, Al-Zaidy S, Shell R, Arnold W, Rodino-Klapac L, Prior T et al. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy.N Engl J Med 2017; 377(18): 1713-1722.
  52. Day J, Mendell J, Mercuri E, Finkel R, Strauss K, Kleyn A et al. Clinical Trial and Post marketing Safety of Onasemnogene Abeparvovec Therapy. Drug Safety 2021; $$: 1109-1119.
  53. Ertl H. Immunogenicity and toxicity of AAV gene therapy. Front Immunol 2022; 13: 975803
  54. United States Food and Drug Administration Adverse Events Reporting System (FAERS) Public Dashboard. Search Zolgensma. [cited 2022 DEC 22) from: https://fis.fda.gov.
  55. Pagliarulo N. Novartis reports deaths of two patients treated with Zolgensma gene therapy. [cited 2022 DEC 22] from: https://www.biopharmadive.com/news/novartis-zolgensma-patient-death-liver-injury/629542/
  56. Coratti G, Cutrona C, Pera M, Bovis F, Ponzano M, Chieppa F et al. Motor function in type 2 and 3 SMA patients treated with Nusinersen: a critical review and meta-analysis. Orphanet J Rare Dis 2021; 16:430.
  57. Genentech. New Data for Genentech’s Evrysdi (risdiplam) Demonstrates Long-Term Efficacy and Safety in a Broad Population of People with Spinal Muscular Atrophy [cited 2022 DEC 29] fromhttps://www.gene.com/media/press-releases/14945/2022-03-15/new-data-for-genentechs-evrysdi-risdipla
  58. Ribero V, Daigl M, Marti Y, Gorni K, Evans R, Scott A et al. How does risdiplam compare with other treatments for Types 1-3 spinal muscular atrophy: a systematic literature review and indirect treatment comparison. J Comp Eff Res 2022; 11(5): 347-370.
  59. Hordeaux J, Buza E, Dyer C, Goode T, Mitchell T, Richman L et al. Adeno-Associated Virus Induced Dorsal Root Ganglion Pathology.Hum Gene Ther 2021; 31(15 and 16): 808-819.
  60. Buss N, Lanigan L, Zeller J, Cissell D, Metea M, Adams E. Characterization of AAV-mediated dorsal root ganglionopathy. Mol Ther 2022; 24: 342-354.
  61. Sidonio R, Pipe S, Callaghan M, Valentino L, Monahan P, Croteau S. Discussion investigational AAV gene therapy with hemophilia patients: A guide. Blood Rev 2021; 47:100759.
  62. Mannucci P. Hemophilia treatment innovations: 50 years of progress and more to come. J Thromb Haemost 2023; 21: 403-412.
  63. Murphy L, Schwartz T, Helmick C, Renner J, Tudor G, Koch G et al. Lifetime Risk of Symptomatic Knee Osteoarthritis. Arthritis Rheum 2008; 59(9): 1207-1213.