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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:2303.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Intramuscular Administration of AAV1-Lipoprotein Lipase^S447X Lowers Triglycerides in Lipoprotein Lipase–Deficient Patients

Erik S. Stroes; Melchior C. Nierman; Janneke J. Meulenberg; Remco Franssen; Jaap Twisk; C. Pieter Henny; Mario M. Maas; Aeilko H. Zwinderman; Colin Ross; Eleonora Aronica; Katherine A. High; Marcel M. Levi; Michael R. Hayden; John J. Kastelein; Jan Albert Kuivenhoven

From Vascular Medicine (E.S.S., M.C.N., R.F., J.J.K., J.A.K.), the Departments of Anaesthesiology (C.P.H.), Radiology (M.M.M.), Biostatistics (A.H.Z.), and (Neuro)pathology (E.A.), and Internal Medicine (M.M.L.), AMC, the Netherlands; Amsterdam Molecular Therapeutics (J.J.M., J.T.), the Netherlands; the Centre for Molecular Medicine and Therapeutics (C.R., M.R.H.), University of British Columbia, Vancouver, Canada; and Children’s Hospital (K.A.H.), University of Pennsylvania School of Medicine, Philadelphia.

Correspondence to J.J.P. Kastelein, AMC, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands. E-mail j.s.jansen@amc.uva.nl

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Lipoprotein lipase (LPL) deficiency is a monogenetic disorder that underlies persistently elevated triglyceride (TG) levels and consequently predisposes patients to potentially life-threatening pancreatitis. In view of the absence of adequate therapy, we developed a gene replacement strategy to lower TG levels in these patients.¹ This report summarizes the data of a first clinical trial (CT-AMT-010-01) in LPL-deficient individuals after intramuscular administration of a viral vector. In a 3-month open-label study, LPL^S447X-adeno-associated virus subtype 1(AAV1) vector^1,2 was injected in the leg musculature of 8 LPL-deficient patients at a dose of 1x10¹¹ (n=4) or 3x10¹¹ (n=4) genome copies per kilogram body weight (40 and 60 injections of 500 microliters, respectively). Primary objectives were to establish efficacy and safety of intramuscular application of this vector. The primary outcome measure was to achieve a reduction in individual median fasting plasma TG to a level equal to or less than 10 mmol/L on top of diet, or to achieve a reduction in median fasting plasma TG equal to or more than 40% on top of diet.

The treatment was well tolerated and no serious adverse events were observed. At 12 weeks, all patients presented with a decrease of median TG levels compared to baseline TG (P<0.007 versus baseline; Figure, a and b), corresponding to a mean TG reduction of 27% and 41% in low- and higher-dose group, respectively (Figure, c and d). One patient in the low-dose and 3 patients in the high-dose group reached . . . [Full Text of this Article]

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