Early miglustat therapy in infantile Niemann-Pick disease type C.
Niemann-Pick disease type C is a rare inherited cholesterol trafficking disorder, where impaired intracellular lipid transport leads to storage of unesterified cholesterol and glycosphingolipids in many tissues, including the brain. Substrate reduction therapy with miglustat, an iminosugar that inhibits glycosphingolipid synthesis, was proposed to treat Niemann-Pick disease type C, based on evidence of slower disease progression and prolonged survival in animal models. Miglustat was subsequently approved in Europe to treat progressive neurologic manifestations in both children and adults in early 2009, based on clinical study data. We report on the early treatment of two pediatric Niemann-Pick type C patients with miglustat. Patient 1, a 7.5-year-old girl with early-infantile onset, began receiving miglustat at age 7 months. Patient 2, the brother of a girl diagnosed with late-infantile onset Niemann-Pick type C, began receiving miglustat at age 19 months, when he was asymptomatic for neurologic disease. After 7 and 5 years of miglustat therapy, respectively, both patients remain free of neurologic manifestations. These findings suggest that miglustat may be more effective if used to prevent, rather than treat, neurologic manifestations in infantile-onset Niemann-Pick type C.
Unit of Rare Diseases, Department of Pediatrics, Gaslini Institute, Genoa, Italy. majadirocco@ospedale-gaslini.ge.it
Maja
M
Di Rocco
Andrea
A
Dardis
Annalisa
A
Madeo
Rita
R
Barone
Agata
A
Fiumara
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008137:Longitudinal Studies; D008562:Membrane Glycoproteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy* / Q000235:genetics
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D017485:1-Deoxynojirimycin; C059896:miglustat