Murine Î²-galactosidase stability is not dependent on temperature or protective protein/cathepsin A.

[gm1 gangliosidosis]

GM 1 gangliosidosis , a neurodegenerative disorder , and Morquio B disease , a skeletal disorder , are lysosomal storage disorders caused by inherited defects in the enzyme Î²-galactosidase (GLB 1 ; EC 3 .1 .2 .23 ; MIM #611458 ). Enzyme replacement therapy (ERT ), a standard of care for a number of non-neuronopathic lysosomal storage disorders , is not yet available for GLB 1 deficiency . Although functionally active recombinant human and feline GLB 1 precursors have been purified , ERT has not yet been demonstrated in GM 1 gangliosidosis or Morquio B disease models . A major obstacle to developing effective therapy may be the stability of human GLB 1 . We show here that mouse GLB 1 has greater stability when compared to human GLB 1 , and that human GLB 1 activity is temperature and protective-dependent on protein cathepsin A , while that of mouse GLB 1 is not . These findings may impact on the eventual development of ERT for GLB 1 deficiency . Despite our attempts to improve the extracellular stability of human GLB 1 through sequence modification and the use of chemical chaperone N-butyldeoxygalactonojirimycin , the specific enzyme activity remained well below that of mGLB 1 .

Diseases
Validation

Diseases presenting "glb1 deficiency" symptom

gm1 gangliosidosis

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