Redevelopment and Optimization of an Adeno-Associated Virus Gene Therapy Product for the Treatment of Lipoprotein Lipase Deficiency

Lipoprotein lipase (LPL) is an enzyme that breaks down fats, specifically triglycerides, in the blood. An individual with LPL deficiency, which is cause by a defective gene, will therefore begin developing high triglyceride levels as a child. In time, they will develop life-threatening pancreatitis, a predisposition to heart disease, and ultimately, an increased risk of mortality. Previously, we developed a gene therapy for LPL deficiency that was shown to be safe and effective in clinical trials. In 2012, marketed as Glybera, this treatment became the first gene therapy product in the world to receive regulatory approval. However, its extremely high price (>$1 million/patient) severely limited its use, and in 2017 Glybera was removed from the market. Patients now have no curative treatment for LPL deficiency. A major contributor to the therapy's high cost were the small-scale production methods. As part of the Hayden and Ross lab and in collaboration with the National Research Council of Canada, the aim of my project is to develop and validate a more efficacious and cost-effective Adeno-Associated Virus (AAV)-based gene therapy treatment for LPL deficiency.