Miglustat isindicated to treat adults with mild to moderate type I Gaucher disease for whom enzyme replacement therapy is unsuitable.[14]
In the European Union, miglustat (Opfolda), in combination withcipaglucosidase alfa, is a long-term enzyme replacement therapy in adults with late-onset Pompe disease (acid α‑glucosidase [GAA] deficiency).[10]
Miglustat is contraindicated for people with neurological conditions, kidney problems, women who are pregnant, and men and women planning to conceive a child.[15]
Serious side effects include pain, burning, numbness or tingling in the hands, arms, legs, or feet; shaking hands that cannot be controlled; changes in vision; and easy bruising or bleeding. Common side effects include gastrointestinal effects (including diarrhea, stomach pain or bloating, gas, loss of appetite, weight loss, upset stomach, vomiting, constipation), dry mouth, muscular effects (including weakness, muscle cramps, especially in the legs, feeling of heaviness in the arms or legs, unsteadiness when walking), back pain, dizziness, nervousness, headache, memory problems, and difficult or irregular menstruation (period).[15]
Type I Gaucher's disease is anautosomal recessive disorder; parents are generally healthy carriers with one functional and one mutated (nonfunctioning) copy of the Gaucher disease gene,GBA. People with type I Gaucher have a defect in the enzyme calledglucocerebrosidase (also known as acid β-glucosidase). Glucocerebrosidase is anenzyme, and its function is to convertglucocerebroside (also known asglucosylceramide) into ceramide and glucose. When this enzyme doesn't work, glucocerebroside accumulates, which in turn causes liver and spleen enlargement, changes in the bone marrow and blood, and bone disease. Miglustat functions as a competitive and reversible inhibitor of the enzyme glucosylceramide synthase, the initial enzyme in a series of reactions which results in the synthesis of most glycosphingolipids.[16][17]
Miglustat has been approved in the EU, Canada, and Japan for treating progressive neurological complications in people with Niemann–Pick disease, type C (NPC).[24][25][26][27][28]
On 26 April 2023, theCommittee for Medicinal Products for Human Use (CHMP) of theEuropean Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Opfolda, intended for the treatment of glycogen storage disease type II (Pompe disease) in combination with cipaglucosidase alfa.[10] The applicant for this medicinal product is Amicus Therapeutics Europe Limited.[10] Opfolda is a hybrid medicine of Zavesca which has been authorized in the EU since 2002.[10] Opfolda contains the same active substance as Zavesca but in a lower strength.[10] It is also authorized for a different indication and can only be used in combination with cipaglucosidase alfa.[10] Miglustat (Opfolda) was approved for medical use in the European Union in June 2023.[8][29]
In July 2004, Actelion started a clinical trial of miglustat to treatTay–Sachs disease, particularly late-onset Tay–Sachs with an estimated enrollment of 10 subjects; the trial ended August 2007.[30]
N-butyldeoxynojirimycin interferes with the secretion ofhepatitis B virus[33] and reduces the infectivity ofHIV virions, in the latter case by preventing properfolding of thegp160 precursorglycoprotein to cause a conformational defect in maturegp120, which interferes with the process of fusion with host membranes.[34][35]
^"Yargesa EPAR".European Medicines Agency. 11 April 2023. Retrieved2 October 2023.
^abcdefg"Opfolda: Pending EC decision".European Medicines Agency. 26 April 2023.Archived from the original on 27 April 2023. Retrieved27 April 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^Cox TM, Aerts JM, Andria G, Beck M, Belmatoug N, Bembi B, et al. (2003). "The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type I (non-neuronopathic) Gaucher disease: a position statement".Journal of Inherited Metabolic Disease.26 (6):513–526.doi:10.1023/a:1025902113005.PMID14605497.S2CID6681399.
^Abian O, Alfonso P, Velazquez-Campoy A, Giraldo P, Pocovi M, Sancho J (December 2011). "Therapeutic strategies for Gaucher disease: miglustat (NB-DNJ) as a pharmacological chaperone for glucocerebrosidase and the different thermostability of velaglucerase alfa and imiglucerase".Molecular Pharmaceutics.8 (6):2390–2397.doi:10.1021/mp200313e.PMID21988669.
^Clinical trial numberNCT00672022 for "Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset Gangliosidosis: Single and Steady State Oral Doses" atClinicalTrials.gov
