Defining Natural History: Assessment of the Ability of College Students to Aid in Characterizing Clinical Progression of Niemann-Pick Disease, Type C

Abstract

Niemann-Pick Disease, type C (NPC) is a fatal, neurodegenerative, lysosomal storage disorder. It is a rare disease with broad phenotypic spectrum and variable age of onset. These issues make it difficult to develop a universally accepted clinical outcome measure to assess urgently needed therapies. To this end, clinical investigators have defined emerging, disease severity scales. The average time from initial symptom to diagnosis is approximately 4 years. Further, some patients may not travel to specialized clinical centers even after diagnosis. We were therefore interested in investigating whether appropriately trained, community-based assessment of patient records could assist in defining disease progression using clinical severity scores. In this study we evolved a secure, step wise process to show that pre-existing medical records may be correctly assessed by non-clinical practitioners trained to quantify disease progression. Sixty-four undergraduate students at the University of Notre Dame were expertly trained in clinical disease assessment and recognition of major and minor symptoms of NPC. Seven clinical records, randomly selected from a total of thirty seven used to establish a leading clinical severity scale, were correctly assessed to show expected characteristics of linear disease progression. Student assessment of two new records donated by NPC families to our study also revealed linear progression of disease, but both showed accelerated disease progression, relative to the current severity scale, especially at the later stages. Together, these data suggest that college students may be trained in assessment of patient records, and thus provide insight into the natural history of a disease.

Intrathecal 2-hydroxypropyl-β-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: a non-randomised, open-label, phase 1–2 trial

“…The NSS is a Likert-like scale that assesses severity of clinically relevant signs and symptoms in nine major and eight minor domains (appendix, p 10). 5-7 There are no FDA-approved therapies for NPC1 disease. Although miglustat has been approved by the EMA and other regulatory agencies based on a controlled trial and long-term extension studies, 8-10 there remains an unmet medical need for therapies that more effectively slow the neurological progression of NPC1 disease.…”

Cohort study of neurocognitive functioning and adaptive behaviour in children and adolescents with Niemann‐Pick Disease type C1

“…Yanjanin et al 8 described increasing severity over time since diagnosis, but not age at onset, in 19 historical/retrospective patients and 18 prospective patients (mean age 12y 11mo, range 4-51y). This severity scale has also been utilized by Shin et al 9 to expand the NPC1 patient cohort and description of neurological disease progression. Stampfer et al 10 used the scale along with another to describe cognitive decline as one of the earliest and most frequently documented neurological symptoms of NPC1 disease, further demonstrating the importance of reporting on standardized, descriptive measures of this aspect of disease presentation.…”

Efficient Investigation and Differential Diagnosis of Childhood Onset Niemann-Pick Type C

“…As a result of these obstacles, the average time from initial symptoms to a definite diagnosis is approximately four years. 12 Routine tests (even for metabolic dysfunctions) do not normally include NPC. Consequently, it is often overlooked.…”