Enzyme replacement combinational therapy: effective treatments for mucopolysaccharidoses

ABSTRACT

Introduction

Mucopolysaccharidoses (MPS), as a group of inherited lysosomal storage disorders (LSDs), are clinically heterogeneous and characterized by multi-systemic manifestations, such as skeletal abnormalities and neurological dysfunctions. The currently used enzyme replacement therapy (ERT) might be associated with several limitations including the low biodistribution of the enzymes into the main targets, immunological responses against foreign enzymes, and the high cost of the treatment procedure. Therefore, a suitable combination approach can be considered for the successful treatment of each type of MPS.

Areas covered

In this review, we provide comprehensive insights into the ERT-based combination therapies of MPS by reviewing the published literature on PubMed and Scopus. We also discuss the recent advancements in the treatment of MPS and bring up the hopes and hurdles in the futuristic treatment strategies.

Expert opinion

Given the complex pathophysiology of MPS and its involvement in different tissues, the ERT of MPS in combination with stem cell therapy or gene therapy is deemed to provide a personalized precision treatment modality with the highest therapeutic responses and minimal side effects. By the same token, new combinational approaches need to be evaluated by using drugs that target alternative and secondary pathological pathways.

KEYWORDS:

• Combination therapy
• enzyme replacement therapy
• lysosomal storage disorders
• mucopolysaccharidosis

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Author Contributions

AS, HM, and MA gathered the data and drafted the manuscript. AS and AKH helped in the interpretation of the data. MAR and YO conceived and revised the context and finalized the manuscript. All authors have read the journal’s authorship statement and approved the submission of the manuscript.

Article Highlights

• MPS manifests with a complex pathophysiology and different skeletal and/or neurological complications.

• Monotherapy of MPS often associates with several challenges and obstacles.

• The benefits of enzyme replacement therapies (ERTs) are limited due to pharmacokinetic issues.

• ERTs combined bone marrow transplantation and gene/cell therapy can overcome the limitations.

• MPS combinational therapy protocols should be carefully revisited to provide the best clinical outcomes.

Additional information

Funding

This paper is not funded.