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 manifest...

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Detalles Bibliográficos
Autores: Tomsen-Melero, Judit, Moltó-Abad, Marc, Merlo-Mas, Josep, Díaz-Riascos, Zamira V., Cristóbal-Lecina, Edgar, Soldevila, Andreu, Altendorfer-Kroath, Thomas, Danino, Dganit, Ionita, Inbal, Pedersen, Jan Skov, Snelling, Lyndsey, Clay, Hazel, Carreño, Aida, Corchero, José L., Pulido, Daniel, Casas, Josefina, Veciana, Jaume, Schwartz, Simó, Sala, Santi, Font, Albert, Birngruber, Thomas, Royo, Miriam, Córdoba, Alba, Ventosa, Nora, Abasolo, Ibane, González-Mira, Elisabet
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/375344
Acceso en línea:http://hdl.handle.net/10261/375344
https://api.elsevier.com/content/abstract/scopus_id/85212622716
Access Level:acceso abierto
Palabra clave:Fabry disease
Nanoliposomes
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Descripción
Sumario: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.

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