Gene therapies for mucopolysaccharidoses

Abstract

Current specific treatments for mucopolysaccharidoses (MPSs) include enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT). Both treatments are hampered by several limitations, including lack of efficacy on brain and skeletal manifestations, need for lifelong injections, and high costs. Therefore, more effective treatments are needed. Gene therapy in MPSs is aimed at obtaining high levels of the therapeutic enzyme in multiple tissues either by engrafted gene‐modified hematopoietic stem progenitor cells (ex vivo) or by direct infusion of a viral vector expressing the therapeutic gene (in vivo). This review focuses on the most recent clinical progress in gene therapies for MPSs. The various gene therapy approaches with their strengths and limitations are discussed.

Mission possible: Gene therapy for inherited metabolic diseases

“…14 Rossi and Brunetti-Pierri review the development of ex vivo and in vivo gene therapy approaches for mucopolysaccharidosis (MPS) with detailed sections for MPSI, MPSII, MPSIII, MPSIV and MPSVI. 15 Keshavan et al provide a perspective on the development of gene therapy for primary mitochondrial diseases. 16 Ng et al show the epic journey to develop gene therapy approaches for inherited neurotransmitter defects culminating with the recent approval of eladocagene exuparvovec (Upstaza™) for aromatic L-amino acid decarboxylase (AADC) deficiency in late 2022.…”