Alipogene tiparvovec, an adeno-associated virus encoding the Ser(447)X variant of the human lipoprotein lipase gene for the treatment of patients with lipoprotein lipase deficiency.

摘要: Amsterdam Molecular Therapeutics BV is developing alipogene tiparvovec (Glybera, AMT-011, AAV1-LPLS447X), a Ser(447)X variant of the human lipoprotein lipase (LPL) gene (LPLSer(447)X) in an adeno-associated virus vector, as potential intramuscular therapy for treatment LPL deficiency. Familial deficiency rare, autosomal-recessive disorder metabolism that characterized by severe hypertriglyceridemia with episodes abdominal pain, acute pancreatitis and eruptive cutaneous xanthomatosis. The lack functional patients causes accumulation triglyceride (TG)-rich lipoproteins plasma. LPLSer(447)X associated decreased levels plasma TGs increased HDL cholesterol concentrations compared wild-type LPL. Preclinical studies evaluating mouse model demonstrated long-term, dose-dependent correction lipid abnormalities. first clinical trials appear promising, significant decrease observed 3 months following administration tiparvovec, increase local activity protein after 6 months. In addition, frequency was during 3-year follow-up period. At time publication, phase II/III trial deficiency, being conducted to further support submission MAA EMEA ongoing. compound also under investigation type V hyperlipoproteinemia, Syndrome X non-alcoholic steatohepatitis.