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Alipogene tiparvovec (marketed under the trade name Glybera) is a gene therapy treatment that compensates for lipoprotein lipase deficiency (LPLD), a rare inherited disorder which can cause severe pancreatitis. In July 2012, the European Medicines Agency recommended it for approval, the first recommendation for a gene therapy treatment in either Europe or the United States. The recommendation was endorsed by the European Commission in November 2012.
The adeno-associated virus serotype 1 (AAV1) viral vector delivers an intact copy of the human lipoprotein lipase (LPL) gene to muscle cells. The LPL gene is not inserted into the cell's chromosomes but remains as free floating DNA in the nucleus. The injection is followed by immunosuppressive therapy to prevent immune reactions to the virus.
Data from the clinical trials indicates that fat concentrations in blood were reduced between 3 and 12 weeks after injection, in nearly all patients. The advantages of AAV include apparent lack of pathogenicity, delivery to non-dividing cells, and much smaller risk of insertion compared to retroviruses, which show random insertion with accompanying risk of cancer. AAV also presents very low immunogenicity, mainly restricted to generating neutralizing antibodies, and little well defined cytotoxic response. The cloning capacity of the vector is limited to replacement of the virus's 4.8 kilobase genome.
LPLD is a very rare condition (prevalence worldwide 1–2 per million) and as such its clinical testing has involved unusually small cohort sizes. The first main trial (CT-AMT-011-01) involved just 14 subjects and as of 2015 a total of 27 individuals had been involved in Phase III testing.
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