title: Substrate reduction therapy with miglustat in chronic GM2 gangliosidosis type Sandhoff: results of a 3-year follow-up.
abstract: GM2 gangliosidosis type Sandhoff is caused by a defect of beta-hexosaminidase, an enzyme involved in the catabolism of gangliosides. It has been proposed that substrate reduction therapy using N-butyl-deoxynojirimycin (miglustat) may delay neurological progression, at least in late-onset forms of GM2 gangliosidosis. We report the results of a 3-year treatment with miglustat (100 mg t.i.d) in a patient with chronic Sandhoff disease manifesting with an atypical, spinal muscular atrophy phenotype. The follow-up included serial neurological examinations, blood tests, abdominal ultrasound, and neurophysiologic, cognitive, brain, and muscle MRI studies. We document some minor effects on neurological progression in chronic Sandhoff disease by miglustat treatment, confirming the necessity of phase II therapeutic trials including early-stage patients in order to assess its putative efficacy in chronic Sandhoff disease.
authors.affiliation: Department of Neuroscience, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Masciullo
authors.forename: Massimo
authors.initials: M
authors.lastname: Santoro
authors.forename: Anna
authors.initials: A
authors.lastname: Modoni
authors.forename: Enzo
authors.initials: E
authors.lastname: Ricci
authors.forename: Jerome
authors.initials: J
authors.lastname: Guitton
authors.forename: Pietro
authors.initials: P
authors.lastname: Tonali
authors.forename: Gabriella
authors.initials: G
authors.lastname: Silvestri
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D009460:Neurologic Examination; D011237:Predictive Value of Tests; D012497:Sandhoff Disease / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase
references.citation: Bone Marrow Transplant. 2005 Nov;36(10):925-6
references.pmid: 16151419
references.citation: Biochim Biophys Acta. 2006 Dec;1758(12):2057-79
references.pmid: 16854371
references.citation: Genet Med. 2009 Jun;11(6):425-33
references.pmid: 19346952
references.citation: Expert Opin Investig Drugs. 2001 Mar;10(3):455-66
references.pmid: 11227045
references.citation: Biochim Biophys Acta. 1999 Oct 8;1455(2-3):105-38
references.pmid: 10571007
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Jan 15;877(3):149-54
references.pmid: 19095507
references.citation: Skeletal Radiol. 2008 May;37(5):397-404
references.pmid: 18360752
references.citation: Proc Natl Acad Sci U S A. 1999 May 25;96(11):6388-93
references.pmid: 10339597
references.citation: J Biol Chem. 1994 Mar 18;269(11):8362-5
references.pmid: 8132559
references.citation: Neurology. 2006 Jan 24;66(2):278-80
references.pmid: 16434676
references.citation: Ther Clin Risk Manag. 2009;5:877-87
references.pmid: 19956552
references.citation: J Inherit Metab Dis. 2009 Dec;32 Suppl 1:S307-11
references.pmid: 19898952
references.citation: Mol Genet Metab. 2009 Sep-Oct;98(1-2):215-24
references.pmid: 19595619
references.citation: Eur Neurol. 1996;36(6):378-84
references.pmid: 8954307
references.citation: Mol Genet Metab. 2007 May;91(1):111-4
references.pmid: 17251047
references.citation: J Magn Reson Imaging. 2007 Feb;25(2):433-40
references.pmid: 17260395
references.citation: Lancet. 2000 Apr 29;355(9214):1481-5
references.pmid: 10801168
references.citation: Radiol Med. 2010 Jun;115(4):585-99
references.pmid: 20177980
references.citation: J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):449-56
references.pmid: 16763917
references.citation: Neuropathol Appl Neurobiol. 2002 Oct;28(5):343-57
references.pmid: 12366816
references.citation: J Inherit Metab Dis. 2009 Dec;32 Suppl 1:S289-93
references.pmid: 19898953