1 Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
2 Center of Excellence for Flow Cytometry, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
3 Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
4 Division of Pediatric Nursing, Nursing Department, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
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for hemophilia has evolved in the last 40 years from plasma-based
concentrates to recombinant proteins and, more recently, to non-factor
therapeutics. Along this same timeline, research in adeno-associated
viral (AAV) based gene therapy vectors has provided the framework for
early phase clinical trials initially for hemophilia B (HB) and now for
hemophilia A. Successive lessons learned from early HB trials have
paved the way for current advanced phase trials. Nevertheless,
questions linger regarding 1) the optimal balance of vector dose to
transgene expression, 2) amount and durability of transgene expression
required, and 3) long-term safety. Some trials have demonstrated unique
findings not seen previously regarding transient elevation of liver
enzymes, immunogenicity of the vector capsid, and loss of transgene
expression. This review will provide an update on the clinical AAV gene
therapy trials in hemophilia and address the questions above. A
thoughtful and rationally approached expansion of gene therapy to the
clinics would certainly be a welcome addition to the arsenal of options
for hemophilia therapy. Further, the global impact of gene therapy
could be vastly improved by expanding eligibility to different patient
populations and to developing nations. With the advances made to date,
it is possible to envision a shift from the early goal of simply
increasing life expectancy to a significant improvement in quality of
life by reduction in spontaneous bleeding episodes and disease
To the editor
|Table 1. Demographic
data and laboratory parameters of transfusion-dependent thalassemia
(TDT) subjects, non-transfusion-dependent thalassemia (NTDT) subjects,
|Table 2. Percent red blood cell; RBC (Glycophorin A; GPA), platelet (CD41), endothelium (CD31, 144) and white blood cell (CD11b, CD45) microparticles (MPs) in transfusion-dependent thalassemia (TDT) subjects, non-transfusion-dependent thalassemia (NTDT) subjects, and controls.|
|Table 3. Correlation between antiphospholipid antibodies and percentages of microparticles.|