Annual severity increment score as a tool for stratifying patients with Niemann-Pick disease type C and for recruitment to clinical trials | Orphanet Journal of Rare Diseases | Full Text

Annual severity increment score as a tool for stratifying patients with Niemann-Pick disease type C and for recruitment to clinical trials | Orphanet Journal of Rare Diseases | Full Text

Orphanet Journal of Rare Diseases

Annual severity increment score as a tool for stratifying patients with Niemann-Pick disease type C and for recruitment to clinical trials

• Mario Cortina-BorjaEmail author,
• Danielle te Vruchte,
• Eugen Mengel,
• Yasmin Amraoui,
• Jackie Imrie,
• Simon A. Jones,
• Christine i Dali,
• Paul Fineran,
• Thomas Kirkegaard,
• Heiko Runz,
• Robin Lachmann,
• Tatiana Bremova-Ertl,
• Michael Strupp and
• Frances M. PlattEmail authorView ORCID ID profile

Orphanet Journal of Rare Diseases201813:143

https://doi.org/10.1186/s13023-018-0880-9

©  The Author(s). 2018

• Received: 5 July 2018
• Accepted: 29 July 2018
• Published: 16 August 2018

Abstract

Background

Niemann-Pick disease type C (NPC) is a lysosomal storage disease with a heterogeneous neurodegenerative clinical course. Multiple therapies are in clinical trials and inclusion criteria are currently mainly based on age and neurological signs, not taking into consideration differential individual rates of disease progression.

Results

In this study, we have evaluated a simple metric, denoted annual severity increment score (ASIS), that measures rate of disease progression and could easily be used in clinical practice. We show that ASIS is stable over several years and can be used to stratify patients for clinical trials. It achieves greater homogeneity of the study cohort relative to age-based inclusion and provides an evidence-based approach for establishing inclusion/exclusion criteria. In addition, we show that ASIS has prognostic value and demonstrate that treatment with an experimental therapy - acetyl-DL-leucine - is associated with a reduction in ASIS scores.

Conclusion

ASIS has the potential to be a useful metric for clinical monitoring, trial recruitment, for prognosis and measuring response to therapy.

Keywords

• Niemann-Pick disease type C
• NPC
• Annual severity increment score
• ASIS
• Clinical severity scale
• Clinical trials
• Experimental therapy
• Acetyl-DL-leucine
• Tanganil