Akshay Sharma1, Manu Easow Mathew2, Vasumathi Sriganesh3, Ulrike M Reiss4. 1. Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. 2. South Asian Cochrane Network & Center, Prof. BV Moses Center for Evidence-Informed Health Care and Health Policy, Christian Medical College, Vellore, India. 3. QMed Knowledge Foundation, Mumbai, India. 4. Hematology Department, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
Abstract
BACKGROUND: Haemophilia is a genetic disorder characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy for haemophilia is a curative treatment modality currently under investigation. This is an update of a published Cochrane Review. OBJECTIVES: To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Date of last search: 17 April 2020. SELECTION CRITERIA: Eligible trials include randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation for individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for haemophilia matching the inclusion criteria were identified. MAIN RESULTS: No trials of gene therapy for haemophilia matching the inclusion criteria were identified. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the safety and efficacy of gene therapy for haemophilia. Gene therapy for haemophilia is still in clinical investigation and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.
BACKGROUND:Haemophilia is a genetic disorder characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy for haemophilia is a curative treatment modality currently under investigation. This is an update of a published Cochrane Review. OBJECTIVES: To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Date of last search: 17 April 2020. SELECTION CRITERIA: Eligible trials include randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation for individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for haemophilia matching the inclusion criteria were identified. MAIN RESULTS: No trials of gene therapy for haemophilia matching the inclusion criteria were identified. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the safety and efficacy of gene therapy for haemophilia. Gene therapy for haemophilia is still in clinical investigation and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.
Authors: J Gitschier; W I Wood; T M Goralka; K L Wion; E Y Chen; D H Eaton; G A Vehar; D J Capon; R M Lawn Journal: Nature Date: 1984 Nov 22-28 Impact factor: 49.962
Authors: S Hacein-Bey-Abina; C Von Kalle; M Schmidt; M P McCormack; N Wulffraat; P Leboulch; A Lim; C S Osborne; R Pawliuk; E Morillon; R Sorensen; A Forster; P Fraser; J I Cohen; G de Saint Basile; I Alexander; U Wintergerst; T Frebourg; A Aurias; D Stoppa-Lyonnet; S Romana; I Radford-Weiss; F Gross; F Valensi; E Delabesse; E Macintyre; F Sigaux; J Soulier; L E Leiva; M Wissler; C Prinz; T H Rabbitts; F Le Deist; A Fischer; M Cavazzana-Calvo Journal: Science Date: 2003-10-17 Impact factor: 47.728
Authors: Jerry S Powell; Margaret V Ragni; Gilbert C White; Jeanne M Lusher; Carol Hillman-Wiseman; Tom E Moon; Veronica Cole; Sandhya Ramanathan-Girish; Holger Roehl; Nancy Sajjadi; Douglas J Jolly; Deborah Hurst Journal: Blood Date: 2003-05-22 Impact factor: 22.113
Authors: Marilyn J Manco-Johnson; Thomas C Abshire; Amy D Shapiro; Brenda Riske; Michele R Hacker; Ray Kilcoyne; J David Ingram; Michael L Manco-Johnson; Sharon Funk; Linda Jacobson; Leonard A Valentino; W Keith Hoots; George R Buchanan; Donna DiMichele; Michael Recht; Deborah Brown; Cindy Leissinger; Shirley Bleak; Alan Cohen; Prasad Mathew; Alison Matsunaga; Desiree Medeiros; Diane Nugent; Gregory A Thomas; Alexis A Thompson; Kevin McRedmond; J Michael Soucie; Harlan Austin; Bruce L Evatt Journal: N Engl J Med Date: 2007-08-09 Impact factor: 91.245
Authors: Amit C Nathwani; Edward G D Tuddenham; Savita Rangarajan; Cecilia Rosales; Jenny McIntosh; David C Linch; Pratima Chowdary; Anne Riddell; Arnulfo Jaquilmac Pie; Chris Harrington; James O'Beirne; Keith Smith; John Pasi; Bertil Glader; Pradip Rustagi; Catherine Y C Ng; Mark A Kay; Junfang Zhou; Yunyu Spence; Christopher L Morton; James Allay; John Coleman; Susan Sleep; John M Cunningham; Deokumar Srivastava; Etiena Basner-Tschakarjan; Federico Mingozzi; Katherine A High; John T Gray; Ulrike M Reiss; Arthur W Nienhuis; Andrew M Davidoff Journal: N Engl J Med Date: 2011-12-10 Impact factor: 176.079