Blyscan™ GAG Assay Cited in MPS-IH (Hurler syndrome) In Utero Base Editing Study

Introduction

The Biocolor Blyscan™ Glycosaminoglycan Assay has been cited in Nature Communications in an interesting study by Bose, Sourav K et al. 2021, “In utero adenine base editing corrects multi-organ pathology in a lethal lysosomal storage disease.”

Background

Mucopolysaccharidosis type I (MPS-IH, Hurler syndrome) is a lysosomal storage disease (LSD) that leads to damage of numerous organ systems, usually resulting in early childhood death. This rare genetic disease is caused when a patient carries two defective copies of the IDUA gene, which results in a deficiency of alpha-L-iduronidase enzyme. Alpha-L-iduronidase is necessary for the breakdown of glycosaminoglycans (GAGs) in lysosomes, and in its absence, GAGs accumulate to pathologic levels.

Publication

In the mentioned study, researchers investigated an in utero base editing CRISPR approach that could potentially correct genetic mutations prior to the onset of disease symptoms.

Specifically, the study attempted in utero adeno-associated virus serotype 9 (AAV9) delivery of an adenine base editor (ABE) targeting an IDUA mutation (W392X) in an MPS-IH mouse model.

The therapy resulted in long-term W392X correction in hepatocytes and cardiomyocytes and low-level editing in the brain. Further, subjects showed improved survival and amelioration of metabolic, musculoskeletal, and cardiac disease.

The study results demonstrate a promising approach to pre-birth treatment of MPS-IH, which may be relevant towards treating other genetic diseases as well.

GAGs Measurement

As with human patients with W402X MPS-IH, Idua-W392X mice have increased urine and tissue GAGs level. In the study highlighted above, the Biocolor Blyscan™ Glycosaminoglycan Assay was used to determine GAG content in urine and tissue samples from B6 mice, Idua-W392X mice prenatally injected with AAV.ABE.Idua, and uninjected Idua-W392X mice.

Durable improvement in biochemical parameters in Idua-W392X mice following in utero base editing.
Figure 1. Durable improvement in biochemical parameters in Idua-W392X mice following in utero base editing.

a Urine GAGs were measured monthly in B6 (N = 14), Idua-W392X mice prenatally injected with AAV.ABE.Idua (N = 10 except for month 1, N = 6), and uninjected Idua-W392X mice (N = 14). b, c Tissue GAGs were measured at 6 months of age in the heart and liver (b) and other indicated organs (c) in B6 (N = 14, except for muscle/femur N = 10), prenatally injected mice (N = 10), and uninjected mice (N = 14, except eye, N = 13; and muscle/femur N = 10).

Citation

This content has been adapted from the paper cited below. You can find the entire paper via the link:

Bose, Sourav K et al. “In utero adenine base editing corrects multi-organ pathology in a lethal lysosomal storage disease.” Nature communications vol. 12,1 4291. 13 Jul. 2021, doi:10.1038/s41467-021-24443-8

Product Spotlight

The Biocolor Blyscan™ Glycosaminoglycan Assay is a quantitative dye-binding method for the analysis of sulfated proteoglycans and glycosaminoglycans, (sGAG).

Blyscan Glycosaminoglycan Assay Kit

Test material includes:

  • Cell culture derived material
  • Soluble sGAGs from fluids, such as synovial fluid, urine.
  • Cartilage
  • Connective tissue / tumors

The assay can be used to measure the total sGAG content and can also be adopted to determine the O- and N-sulfated glycosaminoglycan ratio within test samples.

Ilex Life Sciences LLC is an official distributor of Biocolor products. To learn more, please visit the Blyscan™ Glycosaminoglycan Assay product page.