Early skeletal outcomes after hematopoietic stem and progenitor cell gene therapy for Hurler syndrome.

Details

Serval ID
serval:BIB_347F51481FD7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Early skeletal outcomes after hematopoietic stem and progenitor cell gene therapy for Hurler syndrome.
Journal
Science translational medicine
Author(s)
Consiglieri G., Tucci F., De Pellegrin M., Guerrini B., Cattoni A., Risca G., Scarparo S., Sarzana M., Pontesilli S., Mellone R., Gasperini S., Galimberti S., Silvani P., Filisetti C., Darin S., Forni G., Miglietta S., Santi L., Facchini M., Corti A., Fumagalli F., Cicalese M.P., Calbi V., Migliavacca M., Barzaghi F., Ferrua F., Gallo V., Recupero S., Canarutto D., Doglio M., Tedesco L., Volpi N., Rovelli A., la Marca G., Valsecchi M.G., Zancan S., Ciceri F., Naldini L., Baldoli C., Parini R., Gentner B., Aiuti A., Bernardo M.E.
ISSN
1946-6242 (Electronic)
ISSN-L
1946-6234
Publication state
Published
Issued date
05/2024
Peer-reviewed
Oui
Volume
16
Number
745
Pages
eadi8214
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Clinical Trial, Phase II ; Clinical Trial, Phase I ; Research Support, N.I.H., Extramural
Publication Status: ppublish
Abstract
Mucopolysaccharidosis type I Hurler (MPSIH) is characterized by severe and progressive skeletal dysplasia that is not fully addressed by allogeneic hematopoietic stem cell transplantation (HSCT). Autologous hematopoietic stem progenitor cell-gene therapy (HSPC-GT) provides superior metabolic correction in patients with MPSIH compared with HSCT; however, its ability to affect skeletal manifestations is unknown. Eight patients with MPSIH (mean age at treatment: 1.9 years) received lentiviral-based HSPC-GT in a phase 1/2 clinical trial (NCT03488394). Clinical (growth, measures of kyphosis and genu velgum), functional (motor function, joint range of motion), and radiological [acetabular index (AI), migration percentage (MP) in hip x-rays and MRIs and spine MRI score] parameters of skeletal dysplasia were evaluated at baseline and multiple time points up to 4 years after treatment. Specific skeletal measures were retrospectively compared with an external cohort of HSCT-treated patients. At a median follow-up of 3.78 years after HSPC-GT, all patients treated with HSPC-GT exhibited longitudinal growth within WHO reference ranges and a median height gain greater than that observed in patients treated with HSCT after 3-year follow-up. Patients receiving HSPC-GT experienced complete and earlier normalization of joint mobility compared with patients treated with HSCT. Mean AI and MP showed progressive decreases after HSPC-GT, suggesting a reduction in acetabular dysplasia. Typical spine alterations measured through a spine MRI score stabilized after HSPC-GT. Clinical, functional, and radiological measures suggested an early beneficial effect of HSPC-GT on MPSIH-typical skeletal features. Longer follow-up is needed to draw definitive conclusions on HSPC-GT's impact on MPSIH skeletal dysplasia.
Keywords
Humans, Mucopolysaccharidosis I/therapy, Mucopolysaccharidosis I/pathology, Mucopolysaccharidosis I/genetics, Genetic Therapy, Hematopoietic Stem Cell Transplantation, Male, Female, Child, Preschool, Infant, Treatment Outcome, Hematopoietic Stem Cells/metabolism, Child, Bone and Bones/pathology, Magnetic Resonance Imaging
Pubmed
Web of science
Create date
03/05/2024 14:12
Last modification date
26/07/2024 6:01
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