Targeted nanoliposomes to improve enzyme replacement therapy of Fabry disease
The central nervous system represents a major target tissue for therapeutic approach of numerous lysosomal storage disorders. Fabry disease arises from the lack or dysfunction of the lysosomal alpha-galactosidase A (GLA) enzyme, resulting in substrate accumulation and multisystemic clinical manifestations. Current enzyme replacement therapies (ERTs) face limited effectiveness due to poor enzyme biodistribution in target tissues and inability to reach the brain. We present an innovative drug delivery strategy centered on a peptide-targeted nanoliposomal formulation, designated as nanoGLA, engineered to selectively deliver a recombinant human GLA (rhGLA) to target tissues. In a Fabry mouse model, nanoGLA demonstrated improved efficacy, inducing a notable reduction in Gb3 deposits in contrast to non-nanoformulated GLA, even in the brain, highlighting the potential of the nanoGLA to address both systemic and cerebrovascular manifestations of Fabry disease. The EMA has granted the Orphan Drug Designation to this product, underscoring the potential clinical superiority of nanoGLA over authorized ERTs and encouraging to advance it toward clinical translation.
Authors
- Daniel Pulido (ORCID: https://orcid.org/0000-0002-2841-194X)
- Josep Merlo‐Mas (ORCID: https://orcid.org/0000-0002-3698-6655)
- Simó Schwartz (ORCID: https://orcid.org/0000-0001-8297-7971)
- Edgar Cristóbal‐Lecina (ORCID: https://orcid.org/0000-0003-3270-9340)
- Judit Tomsen-Melero (ORCID: https://orcid.org/0000-0002-2837-8107)
- Albert Font (ORCID: https://orcid.org/0000-0003-3908-1111)
- Zamira V. Díaz‐Riascos (ORCID: https://orcid.org/0000-0003-1595-618X)
- Alba Córdoba (ORCID: https://orcid.org/0000-0002-2726-5119)
- Josefina Casas (ORCID: https://orcid.org/0000-0002-7926-5209)
- Thomas Altendorfer‐Kroath (ORCID: https://orcid.org/0000-0001-9531-9505)
- Aida Carreño (ORCID: https://orcid.org/0000-0001-7725-7515)
- José Luís Corchero (ORCID: https://orcid.org/0000-0002-6109-144X)
- Marc Moltó‐Abad (ORCID: https://orcid.org/0000-0002-6364-4570)
- Elisabet González‐Mira (ORCID: https://orcid.org/0000-0003-2502-225X)
- Nora Ventosa (ORCID: https://orcid.org/0000-0002-8008-4974)
- Ibane Abasolo (ORCID: https://orcid.org/0000-0001-5970-6276)
- Jaume Veciana (ORCID: https://orcid.org/0000-0003-1023-9923)
- Thomas Birngruber (ORCID: https://orcid.org/0000-0001-8827-4660)
- Míriam Royo (ORCID: https://orcid.org/0000-0001-5292-0819)
- Inbal Abutbul‐Ionita (ORCID: https://orcid.org/0000-0001-7359-0142)
- Jan Skov Pedersen (ORCID: https://orcid.org/0000-0002-7768-0206)
- Andreu Soldevila
- Dganit Danino (ORCID: https://orcid.org/0000-0002-9782-4940)
- Santi Sala
- Lyndsey Snelling
- Hazel Clay
Institutions
- Universitat Autònoma de Barcelona (ES)
- Joanneum Research (AT)
- Technion – Israel Institute of Technology (IL)
- Aarhus University (DK)
- Instituto de Salud Carlos III (ES)
- LabCorp (United States) (US)
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
- Institute of Advanced Chemistry of Catalonia (ES)
- Vall d'Hebron Hospital Universitari (ES)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
- Institut de Ciència de Materials de Barcelona (ES)
- Guangdong Technion-Israel Institute of Technology (CN)
Publication Details
- Journal
- Science Advances
- Published
- 2024-12-13
- DOI
- https://doi.org/10.1126/sciadv.adq4738
- Citations
- 5
- Primary Topic
- Lysosomal Storage Disorders Research
- Type
- article
- Field-Weighted Citation Impact
- 1.63