Intramuscular Administration of AAV1-Lipoprotein Lipase(S447X) Lowers Triglycerides in Lipoprotein Lipase-Deficient Patients

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, LPLS447X-adeno-associated virus subtype 1(AAV1) vector1,2 was injected in the leg musculature of 8 LPL-deficient patients at a dose of 1×1011 (n=4) or 3×1011 (n=4) genome copies per kilogram body weight (40 and 60 …