title: Neonatal cellular and gene therapies for mucopolysaccharidoses: the earlier the better?
abstract: Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders (LSDs). The increasing interest in newborn screening procedures for LSDs underlines the need for alternative cellular and gene therapy approaches to be developed during the perinatal period, supporting the treatment of MPS patients before the onset of clinical signs and symptoms. The rationale for considering these early therapies results from the clinical experience in the treatment of MPSs and other genetic disorders. The normal or gene-corrected hematopoiesis transplanted in patients can produce the missing protein at levels sufficient to improve and/or halt the disease-related abnormalities. However, these current therapies are only partially successful, probably due to the limited efficacy of the protein provided through the hematopoiesis. An alternative explanation is that the time at which the cellular or gene therapy procedures are performed could be too late to prevent pre-existing or progressive organ damage. Considering these aspects, in the last several years, novel cellular and gene therapy approaches have been tested in different animal models at birth, a highly early stage, showing that precocious treatment is critical to prevent long-term pathological consequences. This review provides insights into the state-of-art accomplishments made with neonatal cellular and gene-based therapies and the major barriers that need to be overcome before they can be implemented in the medical community.
authors.affiliation: Department of Biomedical Research, Alfred I. duPont Institute Hospital for Children, Wilmington, DE, USA. stomatsu@nemours.org.|Skeletal Dysplasia Lab, Department of Biomedical Research, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Rd., Wilmington, DE, 19899-0269, USA. stomatsu@nemours.org.
authors.forename: Shunji
authors.initials: S
authors.lastname: Tomatsu
authors.affiliation: Dulbecco Telethon Institute at Centro Ricerca M. Tettamanti, Department of Paediatrics, University of Milano-Bicocca, San Gerardo Hospital, via Pergolesi, 33, 20900, Monza, MB, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Azario
authors.affiliation: Department of Biomedical Research, Alfred I. duPont Institute Hospital for Children, Wilmington, DE, USA.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sawamoto
authors.affiliation: Dulbecco Telethon Institute at Centro Ricerca M. Tettamanti, Department of Paediatrics, University of Milano-Bicocca, San Gerardo Hospital, via Pergolesi, 33, 20900, Monza, MB, Italy.
authors.forename: Alice Silvia
authors.initials: AS
authors.lastname: Pievani
authors.affiliation: Centro Ricerca M. Tettamanti, Department of Paediatrics, University of Milano-Bicocca, Via Pergolesi, 33, Monza, 20900, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.affiliation: Dulbecco Telethon Institute at Centro Ricerca M. Tettamanti, Department of Paediatrics, University of Milano-Bicocca, San Gerardo Hospital, via Pergolesi, 33, 20900, Monza, MB, Italy. serafinim72@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Serafini
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D042241:Early Diagnosis; D015316:Genetic Therapy; D006801:Humans; D007231:Infant, Newborn; D009083:Mucopolysaccharidoses / Q000235:genetics / Q000628:therapy*; D015997:Neonatal Screening / Q000379:methods