{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T07:58:03Z","timestamp":1773734283245,"version":"3.50.1"},"posted":{"date-parts":[[2024,12,16]]},"group-title":"Physiology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,12,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Absence of functional acid-\u03b1-glucosidase (GAA) leads to early-onset Pompe disease with cardiorespiratory and neuromuscular failure. A novel Pompe rat model (\n                  <jats:italic>\n                    Gaa\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  ) was used to test the hypothesis that neonatal gene therapy with adeno-associated virus serotype 9 (AAV9) restores cardiorespiratory neuromuscular function across the lifespan. Temporal vein administration of AAV9-DES-GAA or sham (saline) injection was done on post-natal day 1; rats were studied at 6-12 months old. Whole-body plethysmography showed that reduced inspiratory tidal volumes in\n                  <jats:italic>\n                    Gaa\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  rats were corrected by AAV-GAA treatment. Matrix- assisted laser desorption\/ionization mass spectrometry imaging (MALDI) revealed that AAV-GAA treatment normalized diaphragm muscle glycogen as well as glycans. Neurophysiological recordings of phrenic nerve output and immunohistochemical evaluation of the cervical spinal cord indicated a neurologic benefit of AAV-GAA treatment.\n                  <jats:italic>In vivo<\/jats:italic>\n                  magnetic resonance imaging demonstrated that impaired cardiac volumes in\n                  <jats:italic>\n                    Gaa\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  rats were corrected by AAV-GAA treatment. Biochemical assays showed that AAV treatment increased GAA activity in the heart, diaphragm, quadriceps and spinal cord. We conclude that neonatal AAV9-DES-GAA therapy drives sustained, functional GAA expression and improved cardiorespiratory function in the\n                  <jats:italic>\n                    Gaa\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  rat model of Pompe disease.\n                <\/jats:p>","DOI":"10.1101\/2024.12.10.627800","type":"posted-content","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T19:11:16Z","timestamp":1734549076000},"source":"Crossref","is-referenced-by-count":2,"title":["Neonatal systemic gene therapy restores cardiorespiratory function in a rat model of Pompe disease"],"prefix":"10.64898","author":[{"given":"David 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