This is a pilot study with the following research aims:

1.) Generation of NMR-based metabolomics data on Niemann-Pick Type C1 (NPC1) disease for identification of metabolic (diagnostic) markers for NPC1 disease at different ages.

2.) Development of methodology to facilitate future work on metabolomics of LCLs.

3.) Evaluation of a 700MHz NMR spectrometer with 1.7mm cryoprobe for metabolomics on mass-limited samples. This instrument is the first of its kind in the UK and offers significant potential for novel metabolomics research. A comparison will be made to data acquired on more standard NMR spectrometers (600MHz with 5mm nitrogen-cooled (Prodigy) probe).

Niemann-Pick type C disease is a complex disorder characterized by elevated cholesterol, glycosphingolipids and sphingosine in endosomal compartments. In the majority of patients lipids are stored due to a defective protein NPC1 a membrane spanning late endosomal protein. A minority (5%) of patients have mutations in a lumenal late endososmal protein NPC2. Although much is known regarding the clinical aspects of NPC disease, the cellular mechanisms leading to neurodegeneration are, to date, poorly understood, and the precise function of the NPC1 and NPC2 proteins remains unknown or speculative. NPC disease has one EMA-approved therapy (Miglustat) which is disease-modifying; however, new, additional therapeutic approaches are urgently required. In order to evaluate these, the identification of novel, clinically-relevant biomarkers for the monitoring of this disease and its progression are necessary.