{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:07:16Z","timestamp":1788966436183,"version":"build-2803163510"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Repurposing therapeutic treatments for diabetes may be a promising strategy for the treatment of neurodegenerative disorders. Intranasal insulin (INI) is shown to improve memory, attention, and cognition in Alzheimer\u2019s dementia. Associations between the etiology of Parkinson\u2019s Disease (PD), brain glucose hypometabolism, and central insulin resistance suggest INI as a promising treatment for PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A phase II single center, randomized, double-blind clinical trial was conducted in 30 participants with PD, aged 41\u201389, MoCA \u2265 16, on a stable dose of anti-PD medications. Participants were randomized to receive intranasal treatment for 21\u202fdays with either placebo, or 20, 40, or 80\u202fIU of regular insulin (INI) using SipNose intranasal device. Primary outcomes of safety and tolerability were assessed in 30 participants by monitoring hypoglycemia, weight, and adverse events. Cognitive, mood, and motor measures were collected pre- and post-treatment for secondary outcome analysis and assessed in 28 participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No significant changes in weight or serum insulin were observed during the study. No hypoglycemic values (&amp;lt;70\u202fmg\/dL) were recorded 15 or 30\u202fmin post-IN dose. Nasal irritation and nosebleeds were the most common adverse events, with most categorized as \u201cmild.\u201d Several secondary outcomes (e.g., verbal fluency and recall) improved from baseline in the 40\u202fIU\/INI arm only, though not significantly more than in the placebo arm. No other outcomes assessed (mood, apathy, motor) improved under INI treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>INI exhibits an acceptable safety profile in patients with PD. Further studies to investigate if INI has a positive impact on cognitive and motor symptoms in PD are warranted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/study\/NCT04251585<\/jats:ext-link>\n                      Identifier, NCT04251585.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1875165","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:08:20Z","timestamp":1788962900000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and tolerability of intranasal insulin in Parkinson\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Julia C.","family":"Johnson","sequence":"first","affiliation":[{"name":"Struthers Parkinson\u2019s Center at HealthPartners","place":["St Paul, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavani","family":"Kashyap","sequence":"additional","affiliation":[{"name":"Struthers Parkinson\u2019s Center at HealthPartners","place":["St Paul, MN, United States"]},{"name":"HealthPartners Institute","place":["Bloomington, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally K.","family":"Gustafson","sequence":"additional","affiliation":[{"name":"HealthPartners Institute","place":["Bloomington, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Struthers Parkinson\u2019s Center at HealthPartners","place":["St Paul, MN, United States"]},{"name":"HealthPartners Institute","place":["Bloomington, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"William 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