title: Effect of alipogene tiparvovec (AAV1-LPL(S447X)) on postprandial chylomicron metabolism in lipoprotein lipase-deficient patients.
abstract: BACKGROUND
  Lipoprotein lipase-deficient (LPLD) individuals display marked chylomicronemia and hypertriglyceridemia associated with increased pancreatitis risk. The aim of this study was to determine the effect of i.m. administration of an adeno-associated viral vector (AAV1) for expression of LPL(S447X) in muscle (alipogene tiparvovec, AAV1-LPL(S447X)) on postprandial chylomicron metabolism and on nonesterified fatty acid (NEFA) and glycerol metabolism in LPLD individuals.
  
  
  METHODS
  In an open-label clinical trial (CT-AMT-011-02), LPLD subjects were administered alipogene tiparvovec at a dose of 1 × 10(12) genome copies per kilogram. Two weeks before and 14 wk after administration, chylomicron metabolism and plasma palmitate and glycerol appearance rates were determined after ingestion of a low-fat meal containing (3)H-palmitate, combined with (continuous) iv infusion of [U-(13)C]palmitate and [1,1,2,3,3-(2)H]glycerol.
  
  
  RESULTS
  After administration of alipogene tiparvovec, the triglyceride (TG) content of the chylomicron fraction and the chylomicron-TG/total plasma TG ratio were reduced throughout the postprandial period. The postprandial peak chylomicron (3)H level and chylomicron (3)H area under the curve were greatly reduced (by 79 and 93%, 6 and 24 h after the test meal, respectively). There were no significant changes in plasma NEFA and glycerol appearance rates. Plasma glucose, insulin, and C-peptide also did not change.
  
  
  CONCLUSIONS
  Intramuscular administration of alipogene tiparvovec resulted in a significant improvement of postprandial chylomicron metabolism in LPLD patients, without inducing large postprandial NEFA spillover.
authors.affiliation: Department of Medicine, Division of Endocrinology, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4. andre.carpentier@usherbrooke.ca
authors.forename: André C
authors.initials: AC
authors.lastname: Carpentier
authors.forename: Frédérique
authors.initials: F
authors.lastname: Frisch
authors.forename: Sébastien M
authors.initials: SM
authors.lastname: Labbé
authors.forename: René
authors.initials: R
authors.lastname: Gagnon
authors.forename: Janneke
authors.initials: J
authors.lastname: de Wal
authors.forename: Stephen
authors.initials: S
authors.lastname: Greentree
authors.forename: Harald
authors.initials: H
authors.lastname: Petry
authors.forename: Jaap
authors.initials: J
authors.lastname: Twisk
authors.forename: Diane
authors.initials: D
authors.lastname: Brisson
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
mesh_terms: D000328:Adult; D002914:Chylomicrons / Q000378:metabolism*; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008071:Lipoprotein Lipase / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019308:Palmitic Acid / Q000097:blood; D019518:Postprandial Period; D016896:Treatment Outcome
chemical_list: D002914:Chylomicrons; D019308:Palmitic Acid; D008071:Lipoprotein Lipase