ライフサイエンスコーパス: alpha-Gal A

1 alpha-Gal A activity in the organs became equal to or hi

2 alpha-Gal A infusions were well tolerated in all patient

3 ase caused by loss of alpha galactosidase A (alpha-Gal A) activity and is characterized by progressiv

4 esults from deficient alpha-galactosidase A (alpha-Gal A) activity and the pathologic accumulation of

5 age disease caused by alpha-galactosidase A (alpha-Gal A) deficiency.

6 -linked deficiency of alpha-galactosidase A (alpha-Gal A).

7 ked inherited loss of alpha-galactosidase A (alpha-Gal A).

8 activity of lysosomal alpha-galactosidase A (alpha-Gal A).

9 ed by a deficiency of alpha-galactosidase A (alpha-Gal A).

10 ed by a deficiency of alpha-galactosidase A (alpha-Gal A).

11 LA gene which encodes alpha-galactosidase A (alpha-Gal A).

12 es upon inhibition of alpha-galactosidase A (alpha-Gal-A) in lysosomes.

13 ry disease (deficient alpha-galactosidase A [alpha-Gal A] activity) were performed in alpha-Gal A-def

14 heart, we found that both organs accumulate alpha-Gal A substrates, including the established biomar

15 ce of tissue and plasma GL-3 by administered alpha-Gal A, thereby providing the in vivo rationale-and

16 By 4 mo of age, alpha-Gal A -/0 mouse aortic endothelial cells achieved

17 ence with G, A, C, or T at nt 9331 within an alpha-Gal A complementary DNA expression vector were pre

18 Both GCase and alpha-Gal A are more stable at lysosomal pH with and wit

19 e results provide insight into how GCase and alpha-Gal A are thermodynamically stabilized by iminosug

20 ted the structure and stability of GCase and alpha-Gal A in a neutral-pH environment reflective of th

21 aortic endothelial cells from wild-type and alpha-Gal A -/0 mice were established.

22 patterns were compared between wild-type and alpha-Gal A null cells.

23 Because alpha-Gal A-deficient mouse models do not recapitulate c

24 -linked lysosomal storage disorder caused by alpha-Gal A (alpha-galactosidase A) deficiency, resultin

25 e synthase, restored cholesterol in cultured alpha-Gal A-deficient mouse aortic endothelial cell cave

26 revealed that the excessive Gb3 in cultured alpha-Gal A-deficient mouse aortic endothelial cells acc

27 apy, engineered to enable robust and durable alpha-Gal A expression.

28 Importantly, cells from alpha-Gal A -/0 mice but not alpha-Gal A +/0 mice expres

29 cultured embryonic fibroblasts derived from alpha-Gal A(-/0) mice were corrected by transducing thes

30 mouse aortic endothelial cells isolated from alpha-Gal A null mice was measured.

31 Thermodynamic parameters obtained from alpha-Gal A unfolding indicate two-state, van't Hoff unf

32 sidase (GCase) and acid-alpha-galactosidase (alpha-Gal A) hydrolyze the sphingolipids glucosyl- and g

33 Recently, we generated alpha-Gal A gene knockout mouse lines and described the

34 The pharmacokinetics and distribution of h-alpha-Gal A mRNA encoded protein in WT mice demonstrated

35 Furthermore, repeat i.v. administration of h-alpha-Gal A mRNA showed a sustained pharmacodynamic resp

36 Single intravenous administration of h-alpha-Gal A mRNA to Gla-deficient mice showed dose-depen

37 rug resistance retroviruses containing human alpha-Gal A cDNA.

38 systemic messenger RNA (mRNA) encoding human alpha-Gal A in wild-type (WT) mice, alpha-Gal A-deficien

39 Preclinical studies of recombinant human alpha-Gal A (r-halphaGalA) infusions in knockout mice de

40 s were determined for four recombinant human alpha-Gal A glycoforms, which differed in sialic acid an

41 Depleting Gb3 with recombinant human alpha-Gal A protein or d-threo-ethylenedioxyphenyl-P4, a

42 By contrast, recombinant human alpha-Gal A was less effective in normalizing the choles

43 - or DGJ-dependent conformational changes in alpha-Gal A are not seen.

44 GLA p.N215S iPSC-CMs were deficient in alpha-Gal A and exhibited globotriaosylceramide accumula

45 globotriaosylceramide levels was observed in alpha-Gal A(-) males treated for 4 weeks with D-t-EtDO-P

46 A [alpha-Gal A] activity) were performed in alpha-Gal A-deficient mice.

47 ng human alpha-Gal A in wild-type (WT) mice, alpha-Gal A-deficient mice, and WT non-human primates (N

48 tly, cells from alpha-Gal A -/0 mice but not alpha-Gal A +/0 mice expressed high levels of the globo-

49 Histopathological analysis of alpha-Gal A -/0 mice revealed subclinical lesions in the

50 The deficiency of alpha-Gal A activity and the accumulation of material co

51 The deficiency of alpha-Gal A leads to the accumulation of its substrates

52 een, and heart with concomitant elevation of alpha-Gal A activity.

53 We report here the generation of alpha-Gal A deficient mice by gene targeting and an anal

54 The knockout mice display a complete lack of alpha-Gal A activity.

55 WT mice demonstrated prolonged half-lives of alpha-Gal A in tissues and plasma.

56 ycin (DGJ), including the first structure of alpha-Gal A with DGJ.

57 Moreover, microbes induced inhibition of alpha-Gal-A activity in antigen-presenting cells.

58 present TLR-dependent negative regulation of alpha-Gal-A as a mechanistic link between pathogen recog

59 When 8-week-old alpha-Gal A(-) males were treated for 8 weeks with 10 mg

60 ted with EXG110 showed dose-dependent plasma alpha-Gal A activity persisting for at least 26 weeks.

61 of EXG110 achieved supraphysiological plasma alpha-Gal A activity and near-complete clearance of accu

62 Recombinant alpha-Gal A more significantly lowered Gb3 levels by 48

63 ated juvenile Fabry mice exhibited sustained alpha-Gal A activity for at least 12 weeks, with the hig

64 Here, we show that alpha-Gal-A deficiency caused vigorous activation of NKT

65 ten falls short of adequately addressing the alpha-Gal A enzyme deficiency in critical tissues, highl

66 57-nucleotide (nt) intronic sequence to the alpha-Gal A transcript from intron 4 of the gene has bee

67 our results with analogous experiments using alpha-Gal A and the chaperone 1-deoxygalactonijirimycin