Role of MYORG in PFBC

Study Name: Defining the hierarchical role of MYORG in the development of Primary Familial Brain Calcification

Name of the researchers: Dr Richard Meek (UK)

Cost/funding of the study: £713,650

Location of Study: University of Southampton

Who can be involved?:

We are always interested in talking to and working with clinicians, especially if they have identified any novel Fahr's disease-associated genes or variants.

Aim of the study:

MYORG is a sugar-processing enzyme made in cells called astrocytes within the brain. Recent converging observations reveal MYORG controls the production of proteins that coordinate phosphate transport in the brain and that aberrant function of MYORG leads to PBC. The mechanistic coupling by which a sugar-processing enzyme regulates phosphate transport is cryptic. PBC patients with mutations in MYORG exhibit the most severe patterns of calcification, even more pronounced than calcification resulting from pathogenic mutations in the phosphate-transporting proteins MYORG regulates. This observation reinforces the idea that MYORG broadly coordinates maintenance of calcium-phosphate homeostasis. No study has investigated PBC gene variants of MYORG, and we hypothesise that these mutations impact the ability of MYORG to produce key calcium-phosphate regulating proteins, rather than a more complex aetiology, e.g. toxic build-up of MYORG aggregates. Evaluating the role of MYORG is paramount in defining the calcium-phosphate regulatory axis in astrocytes and to unpick the molecular underpinnings of PBC. Studies looking at PFC have largely focused on the clinical characterisation, leaving an important knowledge gap where biochemical and molecular biological approaches could redirect research efforts, unveil routes to therapeutic intervention and broaden understanding of mechanisms underlying neurodegeneration. This research will deliver unparalleled insights into MYORG function.

For more information contact: r.w.meek@soton.ac.uk