Intralysosomal Zinc as a biomarker in Fabry disease v1
Research type
Research Study
Full title
Verification of in the vitro finding of elevated intralysosomal zinc in cultured Fabry cells on clinical samples of Fabry patients and the validation of inductively coupled plasma mass spectrometry (ICP-MS) as a method to measure intralysosomal zinc
IRAS ID
327269
Contact name
Duncan Cole
Contact email
Sponsor organisation
Cardiff and Vale University Health Board, University Hospital of Wales
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Fabry disease (FD) is a lysosomal storage disorder, caused by deficiency or absence of α-galactosidase A enzyme activity due to mutations in the GLA gene. This results in accumulation of certain substances in the cells which eventually leads to multi organ damage.
Unpublished data by colleagues from Lloyd-Evans laboratory in Cardiff University in 2019 described in vitro finding of high zinc concentration in the lysosomes of the cultured FD fibroblasts. Our hypothesis is that clinical blood samples obtained from patients with FD show elevated zinc concentration in the lysosomes.
The aims of this study are:
1. Confirm elevated lysosomal zinc in clinical blood samples of patient with FD by qualitative method used at Lloyd-Evans laboratory.
2. Validate inductively coupled plasma mass spectrometry (ICP-MS) method as quantitative method for measurement of lysosomal zinc.
3. Measure lysosomal zinc quantitively using the ICP-MS method.
We will invite 20 healthy volunteers and 50 Fabry patients to participate in this study. We will collect blood samples from each group and isolate the lymphocytes using zinc free isolation kit. We will then measure the zinc in the isolated lymphocytes from both groups qualitatively at Lloyd-Evans lab to confirm elevated zinc in the lysosomes of FD patients in comparison to the controls. This will be followed by validating the ICP-MS method using the same samples and finally quantitatively measure the zinc in FD patients’ samples.
This study will allow the translation of the in vitro finding of elevated lysosomal zinc into a new biomarker that can be used to assess the disease burden at the time of the diagnosis of FD and potentially use this phenotype in the future to assess the patient response to treatment.REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
23/YH/0150
Date of REC Opinion
31 Jul 2023
REC opinion
Further Information Favourable Opinion