Miglustat (Molecule of the Month for August 2012)
Miglustat has been proven to deliver important benefits to people with type 1 Gaucher disease. Dr. Philippe Gaucher first described, in 1882, the symptoms now known as Gaucher Disease. aucher Disease results from a specific enzyme deficiency in the body, caused by a genetic mutation received from both parents. It is an autosomal recessive disease and the most prevalent Lysosomal Storage Disorder (LSD), with an incidence of about 1 in 20,000 live births. It is also the most common genetic disease affecting Ashkenazi Jewish people (Eastern, Central and Northern European ancestry), with a carrier frequency of 1 in 10 (Dr. John Barranger and Dr. Ed Ginns 1989). This pan ethnic disease involves many organ systems, such as liver, spleen, lungs, brain, metabolism and bone marrow.
Miglustat inhibits glucosylceramide synthase, an essential enzyme for the synthesis of most glycosphingolipids (it forms glucosylceramide and accumulates within the macrophages). Miglustat is used to treat adults with mild to moderate type 1 Gaucher disease and it is the first treatment to be approved for patients with Niemann-Pick type C disease. Miglustat may only be used in the treatment of type 1 Gaucher patients for whom enzyme replacement therapy is unsuitable and it's been approved in the European Union for the treatment of progressive neurological manifestations in adult or pediatric patients with Niemann-Pick type C disease (NPC).
In clinical studies, the most common adverse events due to Zavesca included weight loss, diarrhea, and trembling in the hand (tremor). Other common adverse reactions were excess gas (flatulence), abdominal pain, and headache. The most common serious adverse reaction was tingling or numbness in the hands or feet with or without pain (peripheral neuropathy).
Update by Karl Harrison
(Molecule of the Month for August 2012 )