Miglustat: a review of its use in Niemann-Pick disease type C.
Author(s): Lyseng-Williamson KA.
Affiliation(s): Author information:
Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754,
Auckland, New Zealand, demail@springer.com.
Publication date & source: 2014, Drugs. , 74(1):61-74
Miglustat (Zavesca®, Brazaves®), a small iminosugar molecule that reversibly
inhibits glycosphingolipid synthesis, is the only disease-specific drug approved
for the treatment of progressive neurological manifestations of Niemann-Pick
disease type C (NP-C) in adult and paediatric patients. NP-C is a rare,
autosomal-recessive lipid storage disorder characterized by impaired
intracellular lipid trafficking and progressive neurological symptoms leading to
premature death. In a randomized clinical trial, long-term extension studies and
a retrospective observational cohort study, treatment with oral miglustat
stabilized key neurological manifestations of NP-C (including horizontal saccadic
eye movement peak velocity, ambulation, manipulation, language and swallowing) in
paediatric and adult patients with the disease. The therapeutic effects of
miglustat in stabilizing or slowing disease progression have been confirmed in
other reports in the clinical experience setting. The primary tolerability issues
associated with miglustat are mild to moderate gastrointestinal effects (e.g.
diarrhoea, flatulence and abdominal pain/discomfort) and weight loss, which
usually occur during initial therapy and are generally manageable. In the absence
of a cure, miglustat is a valuable agent to reduce the progression of clinically
relevant neurological symptoms in paediatric and adult patients with NP-C, which
is considered a significant achievement in the treatment of this disease.
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