Review of the clinical development of alipogene tiparvovec gene therapy for lipoprotein lipase deficiency.
Alipogene tiparvovec (AAV1-LPL(S447X)) gene therapy is developed to prevent complications and decrease the clinical morbidity of lipoprotein lipase deficiency (LPLD). LPLD is an autosomal recessive disease associated with severe hypertriglyceridemia (hyperTG), severe chylomicronaemia, and low HDL. Acute pancreatitis, the most frequent serious clinical LPLD complication, is a complex and heterogeneous inflammatory condition having many causes including hyperTG and chylomicronaemia. In many patients, low fat diet and currently available lipid lowering drugs are ineffective to prevent hyperTG or pancreatitis in LPLD. The clinical development program of alipogene tiparvovec includes observational studies as well as phase I/II and II/III clinical trials. Pooled data are collected on safety and efficacy issues, including the incidence of pancreatitis.
Gaudet
Daniel
D
Department of Medicine, Université de Montréal, ECOGENE-21 Clinical Research Center, Chicoutimi Hospital, Canada. daniel.gaudet@umontreal.ca
de Wal
Janneke
J
Tremblay
Karine
K
Déry
Stéphane
S
van Deventer
Sander
S
Freidig
Andreas
A
Brisson
Diane
D
Méthot
Julie
J
D000818:Animals; D000229:Dependovirus / Q000235:genetics; D019317:Evidence-Based Medicine; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D007273:Injections, Intramuscular; D008071:Lipoprotein Lipase / Q000096:biosynthesis / Q000235:genetics*; D010195:Pancreatitis / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D018570:Risk Assessment; D016896:Treatment Outcome
C548261:LPL protein, human; D008071:Lipoprotein Lipase