Gene Therapy for Hemophilia B: Achievements, Open Issues, and Perspectives.

Semin Thromb Hemost

Hemophilia Center of the Medical Clinic 2, University Hospital, Frankfurt/Main, Germany.

Published: May 2024

AI Article Synopsis

  • * The FIX Padua variant, which enhances factor IX activity significantly while keeping normal protein levels, has been successful in recent trials, showing good results and promising long-term expression durability.
  • * Despite concerns about immune responses potentially leading to loss of transgene expression and elevated liver enzymes, the overall findings indicate that gene therapy could offer lasting benefits for hemophilia B patients, sustaining factor activity levels for several years.

Article Abstract

Hemophilia B is the first bleeding disorder for which gene therapy clinical programs began. Presently, adenovirus-associated vectors represent the best means to deliver the transgene, and their administration by intravenous route has been used in recent clinical trials. The natural occurring factor IX (FIX) Padua variant, which allows for a 5- to 8-fold higher activity of FIX, while maintaining a normal protein concentration, was subsequently used to enhance the level of transgene expression. All the recent trials using this variant showed good results, and accumulating data suggest that long-term expression durability could be maintained at a significant hemostatic level. However, the risk of loss of transgene expression associated to immune response with liver enzymes elevation remains a concern, especially as to the efficacy and duration of immunosuppressive treatment. Notwithstanding this limitation, the results of clinical trials suggest that gene therapy in hemophilia B has the potential to provide long-term benefits with sustained factor activity levels predicted to last several years in many patients.

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Source
http://dx.doi.org/10.1055/s-0044-1787190DOI Listing

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