Developments in the treatment of hemophilia B: focus on emerging gene therapy

Figures & data

Table 1 Clinical trials for gene therapy of hemophilia

Reference	Year	Vector	Gene delivered	Subjects (n)	Administration	Outcome/comments
Roth et al^Citation32	2001	Plasmid DNA	hFVIII	6	Laparoscopic injection of ex vivo genetically altered fibroblasts into the omentum	Safe and well tolerated. No benefit long-term
Powell et al^Citation33	2003	γ-retroviral	hFVIII	13	Intravenous infusion	Safe and well tolerated. Short-lived circulating FVIII
White and Monahan^Citation34	2005	HD-Ad vector	hFVIII	1	Intravenous infusion	Severe hepatotoxicity and DIC. No detectable FVIII expression
Manno et al^Citation37	2003	AAV2	hFIX	8	Intramuscular injection	Safe and well tolerated. First parenteral administration of rAAV in humans. Circulating FIX levels <1.5%
Manno et al^Citation39	2006	AAV2	hFIX	7	Hepatic artery infusion	Transient transaminitis. FIX expression detected but only transiently with loss of expression concurrent with transaminitis
Nathwani et al^Citation6	2011	AAV8	hFIX	6	Intravenous infusion	Mild, transient transaminitis in only some high dose patients. Stable FIX expression >1% for more than 1 year Effect of transient transaminitis on FIX levels unclear

Abbreviations: AAV, adeno-associated virus; DIC, disseminated intravascular coagulation; hFVIII, human coagulation Factor VIII; hFIX, human Factor IX; HD-Ad, helper-dependent adenovirus; rAAV, recombinant adeno-associated virus.

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PowellJSRagniMVWhiteGCPhase 1 trial of FVIII gene transfer for severe haemophilia A using a retroviral construct administered by peripheral intravenous infusionBlood200310262038204512763932

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MannoCSChewAJHutchisonSAAV-mediated factor IX gene transfer to skeletal muscle in patients with severe haemophilia BBlood200310182963297212515715

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MannoCSPierceGFArrudaVRSuccessful transduction of liver in haemophilia by AAV-Factor IX and limitations imposed by the host immune responseNat Med200612334234716474400

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NathwaniACTuddenhamEGRangarajanSAdenovirus-associated virus vector-mediated gene transfer in haemophilia BN Engl J Med2011365252357236522149959

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