Current advancements in therapy for Niemann-Pick disease: progress and pitfalls

ABSTRACT

Introduction

Niemann-Pick disease type C (NPC) is a rare, autosomal recessive, lysosomal storage disorder. To combat the progressive neurodegeneration in NPC, disease-modifying treatment needs to be introduced early in the course of the disease. The only approved, disease-modifying treatment is a substrate-reduction treatment, miglustat. Given miglustat’s limited efficacy, new compounds are under development, including gene therapy; however, many are still far from clinical use. Moreover, the phenotypic heterogeneity and variable course of the disease can impede the development and approval of new agents.

Areas covered

Here, we offer an expert review of these therapeutic candidates, with a broad scope not only on the main pharmacotherapies, but also on experimental approaches, gene therapies, and symptomatic strategies. The National Institute of Health (NIH) database PubMed has been searched for the combination of the words ‘Niemann-Pick type C’+ ‘treatment’ or ‘therapy’ or ‘trial.’ The website clinicaltrials.gov has also been consulted.

Expert opinion

We conclude a combination of treatment strategies should be sought, with a holistic approach, to improve the quality of life of affected individuals and their families.

KEYWORDS:

• Niemann-Pick Type C
• miglustat
• disease-modifying treatment
• experimental treatment
• neurodegeneration
• symptomatic treatment
• Acetyl-L-Leucine
• arimoclomol

Article highlights

• The treatment with miglustat should be initiated as quickly as possible once the disease is diagnosed.

• Promising, late-stage drug trials are ongoing. These include acetyl-L-leucine and intravenous cyclodextrin.

• Further agents, such as AZ-3102 and efavirenz that warrant further development are in pipeline.

• Agents, including arimoclomol and intrathecal cyclodextrin have undergone late-stage testing and remain active in expanded-access programs.

• Gene therapy and stem cells treatments show efficacy in mouse models of NPC disease. However, the route of administration remains a key factors which needs to be decided.

• A combination of disease-modifying and symptomatic treatments should be sought for.

Declaration of interests

T Bremova-Ertl received honoraria for lecturing from Actelion and Sanofi-Genzyme. She acts as a consultant for Azafaros and Intrabio. She has received grant from Swiss Innovation Agency, University of Bern and Baasch-Medicus. S Schneider received honoraria for lecturing from Actelion. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Author contributions

T Bremova-Ertl: writing of the manuscript. S. Schneider: review of the manuscript.

Additional information

Funding

This paper was not funded.