Gene therapy for lipoprotein lipase deficiency.

PURPOSE OF REVIEW: The present review summarizes the clinical development of adeno-associated viral vector (AAV)1-lipoprotein lipase (LPL)S447X gene therapy (alipogene tiparvovec) for lipoprotein lipase deficiency. Lipoprotein lipase deficiency is a rare inherited disease characterized by severe hypertriglyceridaemia, chylomicronaemia and risk of recurrent pancreatitis or other complications. AAV1-LPLS447X gene therapy is based on the rationale that by adding episomal copies of functional LPL genes into muscle cells lacking active LPL, metabolic function could be improved or restored. RECENT FINDINGS: AAV1-LPLS447X is a nonreplicating and nonintegrating AAV of serotype 1 designed to deliver and express the human LPL gene variant S447X. The clinical development programme for AAV1-LPLS447X consisted of two observational studies, three open-label interventional studies and one case note review analysis. Intramuscular administration of AAV1-LPLS447X was generally well tolerated and was associated with reduction in overall pancreatitis incidence and signs of clinical improvement up to 2 years after administration. Results of interventional studies suggest that markers of postprandial metabolism could be more accurate than fasting plasma triglyceride concentration to monitor the effect of AAV1-LPLS447X . SUMMARY: The overall benefit-risk ratio of AAV1-LPLS447X gene therapy appears positive to date, particularly for the patients presenting the highest risk of complications.