{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:29:50Z","timestamp":1792056590088,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Arginase 1 deficiency (ARG1\u2010D) is an autosomal recessive urea cycle disorder characterised by chronic hyperargininaemia, progressive spasticity, loss of mobility, and cognitive dysfunction. Standard of care (SOC), based on dietary protein restriction, rarely prevents progression. Pegzilarginase, a recombinant human enzyme, is the first approved disease\u2010modifying therapy. We report outcomes from Study 102A (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200914; up to 5\u2009years) and the PEACE long\u2010term extension (LTE) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200931; up to 3\u2009years). Weekly pegzilarginase was administered with SOC. Outcomes included functional mobility (2\u2010\/6\u2010minute walk tests [2MWT\/6MWT], Gross Motor Function Measure [GMFM] D\/E), spasticity (Modified Ashworth Scale [MAS]), plasma arginine, guanidino compounds, and safety. In PEACE, LTE arms were named according to initial 24\u2010week double\u2010blind treatment: placebo\u2013pegzilarginase or pegzilarginase\u2013pegzilarginase. Of 39 evaluable participants, 37 (95%) met composite response or achieved maximum score in \u2265\u20091 motor function domain. In 102A, mean 6MWT improved to 68.2\u2009m (+19%;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912); GMFM\u2010D\/E increased by 2.7\/3.7. In PEACE (pegzilarginase\u2013pegzilarginase; placebo\u2013pegzilarginase), 2MWT improved to 16.5\u2009m (+25%;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096) and 13.5\u2009m (+16%;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092); GMFM\u2010D\/E improved by 4.3\/6.0 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096) and 5.3\/11.3 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093). Spasticity improved in 21\/25 (84%), with 12 reaching MAS 0 (no spasticity). Pegzilarginase sustained plasma arginine control: in 102A, means were 118\u2009\u03bcmol\/L at Week 192 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20099); in PEACE, &lt;\u2009115\u2009\u03bcmol\/L through Week 96 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200911). Guanidinoacetic acid normalised; N\u2010acetylarginine approached normal; argininic acid and \u03b1\u2010keto\u2010\u03b4\u2010guanidinovaleric acid declined by &gt;\u200950%. Most adverse events were mild\/moderate; no treatment\u2010related discontinuations or persistent antibodies occurred. Pegzilarginase produced sustained improvements in mobility, spasticity and biochemical control, supporting early intervention, long\u2010term use and disease modification in ARG1\u2010D.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70066","type":"journal-article","created":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T05:14:55Z","timestamp":1753506895000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Long\u2010Term Efficacy and Tolerability of Pegzilarginase in Arginase 1 Deficiency: Results of Two International Multicentre Open\u2010Label Extension Studies"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0157-8037","authenticated-orcid":false,"given":"Markey","family":"McNutt","sequence":"first","affiliation":[{"name":"UT Southwestern Medical Center  Dallas Texas 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