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

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.

• Authors: Mario Cortina-Borja, 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, Frances M Platt
• Journal: Orphanet journal of rare diseases (Orphanet J Rare Dis) Vol. 13 Issue 1 Pg. 143 (08 16 2018) ISSN: 1750-1172 [Electronic] England
• PMID: 30115089 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Leucine
• acetylleucine

Topics

• Adult
• Clinical Trials as Topic
• Cohort Studies
• Female
• Humans
• Leucine (analogs & derivatives, therapeutic use)
• Lysosomal Storage Diseases (diagnosis, drug therapy)
• Male
• Niemann-Pick Disease, Type C (diagnosis, drug therapy)
• Surveys and Questionnaires
• Young Adult