2026-08-12T20:53:19Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/137282024-11-29T21:38:05Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Bertolin, Joan author Sánchez, Víctor author Ribera, Albert author Jaén, Maria Luisa author Garcia, Miquel author Pujol, Anna author Sánchez, Xavier author Muñoz, Sergio author Marcó, Sara author Pérez, Jennifer author Elias, Gemma author León, Xavier author Roca, Carles author Jimenez, Veronica author Otaegui, Pedro author Navarro, Marc author Ruberte, Jesús author Bosch, Fatima author Mulero, Francisca author 2021-09-09 Mucopolysaccharidosis type IVA (MPSIVA) or Morquio A disease, a lysosomal storage disorder, is caused by N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency, resulting in keratan sulfate (KS) and chondroitin-6-sulfate accumulation. Patients develop severe skeletal dysplasia, early cartilage deterioration and life-threatening heart and tracheal complications. There is no cure and enzyme replacement therapy cannot correct skeletal abnormalities. Here, using CRISPR/Cas9 technology, we generate the first MPSIVA rat model recapitulating all skeletal and non-skeletal alterations experienced by patients. Treatment of MPSIVA rats with adeno-associated viral vector serotype 9 encoding Galns (AAV9-Galns) results in widespread transduction of bones, cartilage and peripheral tissues. This led to long-term (1 year) increase of GALNS activity and whole-body correction of KS levels, thus preventing body size reduction and severe alterations of bones, teeth, joints, trachea and heart. This study demonstrates the potential of AAV9-Galns gene therapy to correct the disabling MPSIVA pathology, providing strong rationale for future clinical translation to MPSIVA patients. Nat Commun. 2021;12(1):5343. 10.1038/s41467-021-25697-y 2041-1723 Nature communications 34504088 http://hdl.handle.net/20.500.12105/13728 ENZYME-REPLACEMENT THERAPY MOUSE MODEL N-ACETYLGALACTOSAMINE-6-SULFATE SULFATASE ELOSULFASE ALPHA KERATAN SULFATE DRUG DELIVERY MURINE MODEL MPS IVA MORQUIO LIVER Treatment of skeletal and non-skeletal alterations of Mucopolysaccharidosis type IVA by AAV-mediated gene therapy.