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
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
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