TY - JOUR T1 - Targeted delivery of acid alpha-glucosidase corrects skeletal muscle phenotypes in Pompe disease mice JF - bioRxiv DO - 10.1101/2020.04.22.051672 SP - 2020.04.22.051672 AU - Andrew D. Baik AU - Philip T. Calafati AU - Nina A. Aaron AU - Antonia Mehra AU - Sven Moller-Tank AU - Lawrence Miloscio AU - Lili Wang AU - Maria Praggastis AU - Matthew S. Birnbaum AU - Cheryl Pan AU - Susannah Brydges AU - Alejandro Mujica AU - Peter Barbounis AU - Nicholas W. Gale AU - Ning Li AU - Christos A. Kyratsous AU - Christopher J. Schoenherr AU - Andrew J. Murphy AU - Aris N. Economides AU - Katherine D. Cygnar Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/04/23/2020.04.22.051672.abstract N2 - Lysosomal diseases are a class of genetic disorders predominantly caused by loss of lysosomal hydrolases, leading to lysosomal and cellular dysfunction. Enzyme Replacement Therapy (ERT), where recombinant enzyme is given intravenously, internalized by cells, and trafficked to the lysosome, has been applied to treat several lysosomal diseases. However, current ERT regimens do not correct disease phenotypes in all affected organs because the biodistribution of enzyme uptake does not match that of the affected cells and tissues that require the enzyme. We present here targeted ERT, an approach that utilizes antibody-enzyme fusion proteins to target the enzyme to specific tissues. The antibody moiety recognizes transmembrane proteins involved in lysosomal trafficking and that are also preferentially expressed in those cells most affected in disease. Using Pompe disease (PD) as an example, we show that targeted ERT is superior to ERT in treating the skeletal muscle phenotypes of PD mice.Competing Interest StatementAll authors were employees of Regeneron Pharmaceuticals, Inc while engaged in the study and may hold stock and/or stock options in the company. A.D.B. and K.D.C. have patent applications for internalizing enzymes and uses thereof. ER -