November 2024 Research Spotlight:

FOCUS ON GAUCHER DISEASE

The third edition of SPOTLIGHT highlights recent scientific publications on Gaucher disease. Authors who have been speakers at WORLDSymposium are noted in bold.

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• 6-O-alkyl 4-methylumbelliferyl-β-D-glucosides as selective substrates for GBA1 in the discovery of glycosylated sterols
  Bannink S, Bila KO, van Weperen J, Ligthart NAM, Ferraz MJ, Boot RG, van der Vliet D, Boer DEC, Overkleeft HS, Artola M, Aerts JMFG.
  J Lipid Res. 2024 Oct 10;65(11):100670. doi: 10.1016/j.jlr.2024.100670. Online ahead of print. PMID: 39395789
• High-throughput screening for small-molecule stabilizers of misfolded glucocerebrosidase in Gaucher disease and Parkinson’s disease
  Williams D, Glasstetter LM, Jong TT, Chen T, Kapoor A, Zhu S, Zhu Y, Calvo R, Gehrlein A, Wong K, Hogan AN, Vocadlo DJ, Jagasia R, Marugan JJ, Sidransky E, Henderson MJ, Chen Y.
  Proc Natl Acad Sci U S A. 2024 Oct 15;121(42):e2406009121. doi: 10.1073/pnas.2406009121. Epub 2024 Oct 10. PMID: 39388267
• Enzyme replacement therapy improves erythropoiesis and iron dysregulation in Gaucher disease
  Motta I, Delbini P, Scaramellini N, Ghiandai V, Duca L, Nava I, Nascimbeni F, Lugari S, Consonni D, Trombetta E, Di Stefano V, Migone De Amicis M, Cassinerio E, Carubbi F, Cappellini MD.
  Ann Hematol. 2024 Oct 7. doi: 10.1007/s00277-024-05918-2. Online ahead of print. PMID: 39370488
• Deletion of Gba in neurons, but not microglia, causes neurodegeneration in a Gaucher mouse model
  Duffy HB, Byrnes C, Zhu H, Tuymetova G, Lee YT, Platt FM, Proia RL.
  JCI Insight. 2024 Nov 8;9(21):e179126. doi: 10.1172/jci.insight.179126. PMID: 39312723
• Striking and widespread microglial activation in the brains of Southdown lambs with type II glucocerebrosidosis (neuronopathic Gaucher disease)
  Finnie J, Hemsley K, Manavis J, Beard H, Brealey J, Robertson T, Blumbergs P.
  J Comp Pathol. 2024 Sep 14;215:10-13. doi: 10.1016/j.jcpa.2024.08.003. Online ahead of print. PMID: 39278040
• Perinatal lethal form Gaucher disease with compound heterozygosity of single nucleotide variants and copy number variations presenting as nonimmune hydrops fetalis and cerebellar hypoplasia: A case report
  Hsu CC, Lee NC, Chien YH, Liu CF, Chang YL.
  Taiwan J Obstet Gynecol. 2024 Sep;63(5):771-776. doi: 10.1016/j.tjog.2024.03.022. PMID: 39266164
• A machine learning model for early diagnosis of type 1 Gaucher disease using real-life data
  Tenenbaum A, Revel-Vilk S, Gazit S, Roimi M, Gill A, Gilboa D, Paltiel O, Manor O, Shalev V, Chodick G.
  J Clin Epidemiol. 2024 Sep 6;175:111517. doi: 10.1016/j.jclinepi.2024.111517. Online ahead of print. PMID: 39245415
• Efficacy of an AAV vector encoding a thermostable form of glucocerebrosidase in alleviating symptoms in a Gaucher disease mouse model
  Milenkovic I, Blumenreich S, Hochfelder A, Azulay A, Biton IE, Zerbib M, Oren R, Tsoory M, Joseph T, Fleishman SJ, Futerman AH.
  Gene Ther. 2024 Sep;31(9-10):439-444. doi: 10.1038/s41434-024-00476-8. Epub 2024 Aug 15. PMID: 39147866
• Gaucher disease provides a unique window into Parkinson disease pathogenesis
  Hertz E, Chen Y, Sidransky E.
  Nat Rev Neurol. 2024 Sep;20(9):526-540. doi: 10.1038/s41582-024-00999-z. Epub 2024 Aug 6. PMID: 39107435
• Presentation of ichthyosis after substrate reduction therapy in Gaucher type 1
  Herbster J, Prada CE, Rasmussen CA, Quadri A, Kuritza V, Viglione M, Hoyer S.
  Am J Med Genet A. 2024 Dec;194(12):e63835. doi: 10.1002/ajmg.a.63835. Epub 2024 Aug 5. PMID: 39101525
• Intrinsic link between PGRN and Gba1 D409V mutation dosage in potentiating Gaucher disease
  Lin Y, Zhao X, Liou B, Fannin V, Zhang W, Setchell KDR, Wang X, Pan D, Grabowski GA, Liu CJ, Sun Y.
  Hum Mol Genet. 2024 Oct 7;33(20):1771-1788. doi: 10.1093/hmg/ddae113. PMID: 39101473
• Patients with Gaucher disease display systemic elevation of ACE2, which is impacted by therapy status and genotype
  Fokra A, Feldman HB, Kurolap A, Kinaneh S, Abassi Z, Hershkovitz T.
  Mol Genet Metab. 2024 Sep-Oct;143(1-2):108534. doi: 10.1016/j.ymgme.2024.108534. Epub 2024 Jul 9. PMID: 39033630
• Histologic and ultrastructural study of intracranial Gaucheroma causing deafness in a patient with Gaucher disease type 3: Effects of substrate reduction therapy
  Yano S, McGowan R, Warren M.
  Mol Genet Metab Rep. 2024 Jun 14;40:101106. doi: 10.1016/j.ymgmr.2024.101106. eCollection 2024 Sep. PMID: 38974840
• Deep learning-based quantification of osteonecrosis using magnetic resonance images in Gaucher disease
  Yu B, Whitmarsh T, Riede P, McDonald S, Kaggie JD, Cox TM, Poole KES, Deegan P; MRC Gaucherite consortium.
  Bone. 2024 Sep;186:117142. doi: 10.1016/j.bone.2024.117142. Epub 2024 Jun 2. PMID: 38834102
• Phenotypic consequences of GBA1 pathological variant R463C (p.R502C)
  Ryan E, Nishimura S, Lopez G, Tayebi N, Sidransky E.
  Am J Med Genet A. 2024 Sep;194(9):e63630. doi: 10.1002/ajmg.a.63630. Epub 2024 Apr 22. PMID: 38647370