Liver-directed gene therapy for fabry disease management
Innovative liver-directed gene therapy aims to treat early and late-onset Fabry disease by enabling hepatocytes to produce alpha-galactosidase A continuously. This approach promises to overcome limitations of current therapies by providing a cost-effective and potentially curative solution.
Overview
This liver-directed gene therapy offers a groundbreaking approach to treating Fabry disease (FD), both in its early and late-onset forms. By transforming hepatocytes into continuous biofactories of alpha-galactosidase A (GLA), the therapy ensures sustained enzyme presence in the bloodstream. This strategy addresses the high costs and variable efficacy of current treatments like enzyme replacement therapy (ERT) by minimizing the risk of anti-GLA antibody formation and maintaining steady enzyme levels.
Technical specifications
The therapy employs two complementary methodologies:
- Genome targeting for early-onset FD: Using CRISPR/Cas9 technology, GLA cDNA is inserted into the albumin gene's open reading frame, ensuring consistent enzyme production in proliferating liver cells.
- AAV-mediated gene therapy for late-onset FD: Leveraging non-integrative adeno-associated virus (AAV) vectors, GLA cDNA is controlled by the a1-AAT promoter/ApoE enhancer, providing long-term expression in non-proliferating liver cells.
This dual approach was validated in Fabry mice, demonstrating restored normal function in a hot-plate test.
Technology readiness level
The current technology readiness level is 4. Proof-of-concept experiments have shown promising results in animal models, with plans for further validation. Upcoming steps include developing mRNA-LNP therapies, longer-term animal studies, and safety assessments, with the ultimate goal of initiating clinical trials.
About International Centre for Genetic Engineering and Biotechnology
The International Centre for Genetic Engineering and Biotechnology is an intergovernmental, non-profit research and training organization operating laboratories in Trieste, New Delhi, and Cape Town. Its campuses provide co-located labs and shared core facilities that enable collaborative R&D, while training and fellowship programs create sustained talent pipelines for partners. Proximity to innovation parks and leading universities at each site, plus biosafety and policy advisory services, helps industry navigate translation and regulatory contexts across regions. Research is supported by member-state contributions and competitive grants from national and international agencies. A dedicated technology transfer office manages IP, licensing, and commercialization across sites.
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