{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:02:08Z","timestamp":1784764928906,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>RNS60 is an investigational product in clinical development for amyotrophic lateral sclerosis (ALS). RNS60 slowed disease progression in the ALS SOD1<jats:sup>G93A<\/jats:sup> mouse model and was safe and well tolerated both in an open\u2010label pilot study and a randomized, placebo\u2010controlled, multicenter phase 2 trial in people living with ALS. The objective of this ongoing expanded access protocol (EAP) was to provide RNS60 to people living with ALS who are ineligible for controlled clinical trials and to collect data on the safety and tolerability of dosing RNS60 via twice\u2010daily nebulization rather than the previously studied daily nebulization with weekly intravenous administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eligible participants (\u2265\u200918\u2009years old, diagnosed with ALS per investigator assessment, and ineligible for an ALS clinical trial testing RNS60) were treated with twice\u2010daily nebulization of RNS60 at home. Safety was evaluated by the assessment of adverse events and routine safety labs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 84 participants have been treated with RNS60 via nebulization twice daily for up to 48\u2009months so far. The most common treatment\u2010related adverse event was increased secretions [<jats:italic>N<\/jats:italic>\u2009=\u200927 (32%)]. Serious adverse events (SAEs) [69 occurrences; <jats:italic>N<\/jats:italic>\u2009=\u200938 (45%) with at least one SAE] and deaths [<jats:italic>N<\/jats:italic>\u2009=\u200924 (28%)] were deemed not related to RNS60.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This EAP supports the benign side effect profile of RNS60 when administered via twice\u2010daily nebulization and demonstrates the feasibility of long\u2010term EAPs as a complementary approach to controlled trials in people with advanced ALS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28398","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T10:21:37Z","timestamp":1742725297000},"page":"124-129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["An Expanded Access Protocol of <scp>RNS60<\/scp> in Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","volume":"72","author":[{"given":"Grace","family":"Addy","sequence":"first","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9427-1452","authenticated-orcid":false,"given":"Erica","family":"Scirocco","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Gelevski","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot","family":"Rohrer","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee","family":"Roderick","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"McCormack","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anat","family":"Weiss Sadan","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Scalia","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Parikh","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Giacomelli","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Sean M. 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