Amsterdam Molecular Therapeutics B.V. reported on data from its lipoprotein lipase (LPL) deficiency program at the American Society of Gene Therapy meeting in Washington, USA. AMT has developed an AAV (serotype 1) vector expressing the LPLS447X variant, which demonstrates high efficacy in a murine model of LPL deficiency.

Intramuscular administration of the AAV1-LPLS447X vector reduced triglyceride levels by over 90%, also visibly noticed by totally cleared plasma. This effect was detected as early as one week after administration, and persisted for over one year. The administration was well tolerated. The results hold promise for the treatment of human LPL deficiency and AMT is now working towards clinical trials. These new data are the result of a collaboration with the group of Professor Michael Hayden at the University of British Columbia, Vancouver, Canada and the Lipid research Group of Professor John Kastelein at the Academic Medical Center (AMC) in Amsterdam, The Netherlands. AMT licensed the LPL technology exclusively from Xenon Genetics Inc, Vancouver, Canada, and the AAV technology from the German Cancer Institute at Heidelberg, Germany (DKFZ).

LPL deficiency is a disorder affecting thousands in the Western world. The disease is caused by deficiency of lipoprotein lipase, the principal enzyme involved in the clearance of triglycerides from the plasma compartment. Humans who are deficient in LPL, develop chronic pancreatitis, ultimately resulting in diabetes mellitus. There is no specific therapy currently available to modulate the course of the illness for these patients other than a severe reduction of dietary fat, which is hard to comply with. Gene therapy offers prospects for effectively treating this disorder as well as correcting the lipoprotein phenotype in coronary artery disease and myocardial ischemia.