iPSC GBA Mutation Model for Gaucher's and Parkinson's Disease

Mutations of the GBA gene are the most prevalent mutations in Parkinson's disease, accounting for 10-25% of the cases. They also cause the rare disease Gaucher's disease. More than 300 mutations of the GBA gene located at 1q21 locus are known.

The GBA gene encodes the enzyme glucocerebrosidase (GCase). GCase metabolizes the glycosphingolipid glucosylceramide into ceramide and glucose. Glycosphingolipids are essential for the lipid membrane of neurons.

A decrease in the activity of glucocerebrosidase increases alpha-synuclein and phosphorylated alpha-synuclein. Glucocerebrosidase inactivity also alters the calcium homeostasis involved in the electrophysiological activity. GBA mutation involvement is well observed in cortical areas of the brain.

To model diseases caused by GBA mutations, we use human induced pluripotent stem cell-derived neuronal cell cultures on microelectrode arrays.

For general information on iPSC-derived neuronal cell cultures, see our page on neural stem cells.

GBA mutation assay with iPSC derived glutamatergic cells

The NeuroProof GBA mutation assays work with ioGlutamatergic cells from bit.bio. Several mutations of the GBA gene are available, including the known N370S mutation.

Currently, we have a GBA null/null mutation in place and its isogenic control that we offer for screening.

The GBA null/null mutation shows a hyperexcited behavior in comparison to wild-type neurons.

iPSC development with GBA mutation

Image: Development of electrical activity over 35 div of ioGlutamatergic neurons of wild-type (yellow) and GBA null/null mutant (blue) neurons show a significant hyperexcited activity of diseased cells.

Our Service

For your screening project, we deliver the most relevant screening assay. Please discuss your needs with our experts so that we can provide an appealing proposal.

You can select between different available heterozygous and homozygous mutations. There are several positive control compounds like chaperones or HDAC modulators, and CBE as a negative control.

Comparing results from different mutations will increase your predictive power dramatically.