Targeted delivery of acid alpha-glucosidase corrects skeletal muscle phenotypes in Pompe disease mice
Andrew D. Baik,
Philip T Calafati,
Nina A. Aaron,
Matthew S Birnbaum,
Nicholas W. Gale,
Christopher J Schoenherr,
Andrew J Murphy,
Aris N Economides,
Katherine D. Cygnar
Posted 23 Apr 2020
bioRxiv DOI: 10.1101/2020.04.22.051672
Posted 23 Apr 2020
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 Statement All 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.
- Downloaded 375 times
- Download rankings, all-time:
- Site-wide: 62,535
- In bioengineering: 1,150
- Year to date:
- Site-wide: None
- Since beginning of last month:
- Site-wide: 30,092
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!