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Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial.

ABSTRACT: We describe the 2-year follow-up of an open-label trial (CT-AMT-011-01) of AAV1-LPL(S447X) gene therapy for lipoprotein lipase (LPL) deficiency (LPLD), an orphan disease associated with chylomicronemia, severe hypertriglyceridemia, metabolic complications and potentially life-threatening pancreatitis. The LPL(S447X) gene variant, in an adeno-associated viral vector of serotype 1 (alipogene tiparvovec), was administered to 14 adult LPLD patients with a prior history of pancreatitis. Primary objectives were to assess the long-term safety of alipogene tiparvovec and achieve a ?40% reduction in fasting median plasma triglyceride (TG) at 3-12 weeks compared with baseline. Cohorts 1 (n=2) and 2 (n=4) received 3 × 10(11)?gc?kg(-1), and cohort 3 (n=8) received 1 × 10(12)?gc?kg(-1). Cohorts 2 and 3 also received immunosuppressants from the time of alipogene tiparvovec administration and continued for 12 weeks. Alipogene tiparvovec was well tolerated, without emerging safety concerns for 2 years. Half of the patients demonstrated a ?40% reduction in fasting TG between 3 and 12 weeks. TG subsequently returned to baseline, although sustained LPL(S447X) expression and long-term changes in TG-rich lipoprotein characteristics were noted independently of the effect on fasting plasma TG.

SUBMITTER: Gaudet D

PROVIDER: S-EPMC4956470 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial.

Gaudet D D Méthot J J Déry S S Brisson D D Essiembre C C Tremblay G G Tremblay K K de Wal J J Twisk J J van den Bulk N N Sier-Ferreira V V van Deventer S S

Gene therapy 20120621 4

We describe the 2-year follow-up of an open-label trial (CT-AMT-011-01) of AAV1-LPL(S447X) gene therapy for lipoprotein lipase (LPL) deficiency (LPLD), an orphan disease associated with chylomicronemia, severe hypertriglyceridemia, metabolic complications and potentially life-threatening pancreatitis. The LPL(S447X) gene variant, in an adeno-associated viral vector of serotype 1 (alipogene tiparvovec), was administered to 14 adult LPLD patients with a prior history of pancreatitis. Primary objec ...[more]

PMID: 22717743

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Dataset Information

Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial.

Publications

Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial.

Similar Datasets

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