Parkinson’s & Gaucher disease
with GBA mutation

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Performing measurements of

GBA1 Protein in CSF & Plasma with ultra sensitivity

GCase activity using selective GCase substrate

GlcCer/GlcSph & GalCer/GalSph and α and β separation with ultra sensitivity

Role of GBA1 / GCase in Parkinson’s and Gaucher Diseases

As one of the most common risk factors, the mutation of Glucosylceramidase beta 1 (GBA1) plays an integral role when discussing Parkinson’s Disease (PD) and Gaucher Disease (GD). GBA1 is a gene responsible for encoding GCase (also called β-Glucocerebrosidase, or acid β-glucosidase, D-glucosyl-N-acylsphingosine glucohydrolase), an enzyme active in lysosomes that helps its “recycling center” break down lipids and glycolipids. However, if GCase activity diminishes due to mutations in the GBA1 allele(s), it can ultimately lead to an accumulation of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph), a cataclysmic combination that accelerates brain neuron cell degeneration. More specifically, homozygous and heterozygous mutations in the GBA gene increase the risk of Gaucher and Parkinson’s, respectively.

Drug Efficacy

In order to better assess drug efficacy, Nextcea quantitates and integrates GBA1, GCase, GlcCer, and GlcSph data with the endolysosomal pathway for neurodegenerative clinical and non-clinical studies.

GBA1 Protein Measurement in CSF & Plasma

Nextcea is capable of quantitating GBA1 to uniquely low levels for Parkinson’s or Gaucher patients.

GCase activity measuring capability

Nextcea has developed a GCase selective substrate “Gmetry” that GCase strongly and specifically favors. Rather than a non-specific hydrolyzation of GlcCer or fluorescent substrates (such as 4-Methylumbelliferyl β-D-glucopyranoside [4MU-β-glc] and resorufin-β-D-glucopyranoside) by GCases 1, 2, 3, our substrate “Gmetry” specifically reacts with the active site of GCase.

GlcCer/GlcSph & GalCer/GalSph α and β stereoisomer separation and measurement

Nextcea can identify, separate, GlcCer/GlcSph from GalCer/GalSph as well as measure α and β isoforms of GlcCer and GlcSph down to 1 pg/mL, equivalent to a sensitivity of 1 in a trillion.

Additionally, Nexcea offers the ability to measure concentration across human and animal biological matrices–such as CSF, plasma, urine, and tissues–for any of the following GCase pathway:

References

  1. Merchant et al (2023) LRRK2 and GBA1 variant carriers have higher urinary bis(monacylglycerol) phosphate concentrations in PPMI cohorts 9:30; https://doi.org/10.1038/s41531-023-00468-2
  2. Surface M et al (2021) Plasma Glucosylsphingosine in GBA1 Mutation Carriers with and without Parkinson’s disease. Movement Disorders, 37(2):416-421