Ashlee R. Stiles

Prospective analysis and continued monitoring of plasma deacylated glucosylceramide (GlcSph) in patients with Gaucher disease · April 1, 2020 - March 31, 2022 Awarded by: Shire/Takeda · $243,073.00 There are two main components of the research plan, to be conducted under this continued grant funding: 1. Prospective analysis of GlcSph and correlation with clinical findings on patients with Gaucher disease consented and enrolled in our existing study ‘Genetic Disease Repository for Blood, Urine and Tissue’ (Duke IRB # Pro00007612) and attending the Duke Metabolic Clinics (PI: Priya Kishnani, MD). This will be achieved by measurement of GlcSph in patient’s naïve to treatment and patients currently on treatment (ERT or SRT), and correlation of GlcSph with clinical phenotype and routinely measured analytes. As mentioned above, we observed a correlation of GlcSph with historical biomarkers including chitotriosidase activity (CHITO), angiotensin-converting enzyme (ACE), and tartrate resistant acid phosphatase (TRAP). We plan to expand upon this with additional phenotyping of the current population to include: leukocyte count, hemoglobin, platelets, MCV, MCH, calcium, alkaline phosphatase, vitamin D, D-dimer, ferritin, lipids, ultrasound or volumetric MRI, bone assessment through regular DEXA/serial x-rays (every 3 years). Additionally, we would also monitor growth parameters (height, weight, and BMI) in our pediatric population. 2. To expand the number of subjects by collaborating with Emory HealthCare, Division of Medical Genetics. Emory will recruit patients with Gaucher disease and procure plasma samples from consented patients for GlcSph analysis to perform correlations with clinical and laboratory test information. Three years of additional funding will allow for long-term monitoring over 5 consecutive years (2 year current retrospective analysis study + 3 years of prospective analysis study) for Gaucher patients already included in the study, and for expansion of the cohort through new recruitment from Duke and Emory Health Systems.

Development of deacylated glucosylceramide (lyso-Gb1) biomarker in plasma samples from Gaucher disease patients and evaluating its’ feasibility in monitoring patients on therapy. · April 1, 2018 - March 31, 2020 Awarded by: Shire Pharmaceuticals · $218,455.00 To develop and validate an assay for plasma deacylated glucosylceramide (lyso-Gb1) by UPLC-MS/MS and to investigate the utility of lyso-Gb1 as a disease severity biomarker in Gaucher disease and for monitoring treatment efficacy. This will be achieved by measurement of lyso-Gb1 in naïve and treated patients, and correlation of lyso-Gb1 with the disease severity, and with other routine biomarkers including chitotriosidase activity, angiotensin-converting enzyme (ACE), and tartrate resistant acid phosphatase (TRAP).