Enzyme replacement therapy for mucopolysaccharidoses; past, present, and future

Area of Science:

• Biochemistry
• Genetics
• Pharmacology

Background:

• Mucopolysaccharidoses (MPS) are lysosomal storage disorders requiring enzyme replacement therapy (ERT).
• Current ERT offers benefits like immediate treatment but has limitations including poor brain and cartilage penetration, lengthy infusions, and high costs.
• Existing ERT shows limited efficacy in neurological, cardiovascular, and skeletal disease progression.

Purpose of the Study:

• To review the efficacy and limitations of current ERT for MPS.
• To describe novel ERT strategies designed to overcome conventional treatment obstacles.
• To explore new approaches for improving ERT delivery to the brain and avascular tissues.

Main Methods:

• Literature review of current and emerging ERT strategies for MPS.
• Analysis of ERT limitations, focusing on delivery to specific tissues like the brain and cartilage.
• Summary of novel ERT technologies, including antibody-mediated delivery, protein complexes, and bone-targeting approaches.

Main Results:

• Current ERT has demonstrated limited success in addressing severe MPS manifestations, especially in neurological and musculoskeletal systems.
• Novel ERT strategies are being developed to enhance enzyme delivery across the blood-brain barrier and into avascular tissues.
• Targeted ERT approaches, such as bone-targeting therapies for MPS IVA and VI, show potential for improved efficacy.

Conclusions:

• Conventional ERT for MPS has significant limitations that impact therapeutic outcomes.
• Emerging ERT technologies hold promise for overcoming current treatment barriers and improving patient prognosis.
• Future research should focus on optimizing ERT delivery mechanisms for enhanced treatment of MPS-related complications.