Intranasal insulin for improving cognitive function in multiple sclerosis
Cognitive impairment is common in people with multiple sclerosis (PwMS). There is an urgent need to identify/develop novel therapies that can help cognitive function in MS. Insulin is critical for helping with regulation of multiple CNS functions, including learning and memory. Insulin administrated...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-07-01
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| Series: | Neurotherapeutics |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878747925000595 |
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| author | Scott D. Newsome Kathryn C. Fitzgerald Abbey Hughes Meghan Beier Jacqueline Koshorek Yujie Wang Daniela Pimentel Maldonado Thomas Shoemaker Taimur Malik Tarik Bayu Pablo E. Ravenna Ama Avornu Elias S. Sotirchos Meghan Romba John Muschelli Todd T. Brown Peter A. Calabresi Ellen M. Mowry |
| author_facet | Scott D. Newsome Kathryn C. Fitzgerald Abbey Hughes Meghan Beier Jacqueline Koshorek Yujie Wang Daniela Pimentel Maldonado Thomas Shoemaker Taimur Malik Tarik Bayu Pablo E. Ravenna Ama Avornu Elias S. Sotirchos Meghan Romba John Muschelli Todd T. Brown Peter A. Calabresi Ellen M. Mowry |
| author_sort | Scott D. Newsome |
| collection | DOAJ |
| description | Cognitive impairment is common in people with multiple sclerosis (PwMS). There is an urgent need to identify/develop novel therapies that can help cognitive function in MS. Insulin is critical for helping with regulation of multiple CNS functions, including learning and memory. Insulin administrated intranasally has shown to improve memory and learning in healthy people and in those with some neurodegenerative disorders. Hence, there was rationale for investigating intranasal insulin in PwMS who experience cognitive impairment. We completed a phase Ib/II, randomized, double-blind, placebo-controlled trial; participants were randomized in a 1:1:1 fashion, stratified by relapsing versus progressive MS, to intranasal insulin 10 international units (IU) twice a day, 20 IU twice a day, or placebo for 24 weeks. One-hundred and five PwMS were enrolled, 69 of whom had at least one follow up visit during the active treatment phase of the trial (baseline to week 24). The cohort's mean age was 52.4 ± 9.7years, 62 % were female, and ∼60 % had relapsing-remitting MS. The most common side effects amongst treatment groups included headache, rhinorrhea, and dizziness. There were 13 SAEs which were not deemed study drug related; there were no deaths. The main clinical outcome measure, SDMT, did not demonstrate any difference between intranasal insulin and placebo. Similar findings were noted for all secondary outcome measures. Intranasal insulin appeared safe and well-tolerated in PwMS. However, it was not superior to placebo in any of the clinical outcome measures assessed, which could have been impacted by the duration of the trial, small sample size for a three-arm trial design, data missingness (particularly during COVID-19), outcome measure insensitivity to change, baseline cognitive reserve, or other factors. Nonetheless, intranasally-administered therapeutics may be of interest to develop further as a way to get across the blood brain barrier. |
| format | Article |
| id | doaj-art-7e42b1ac2aa24c0ca9389a97c500294e |
| institution | Kabale University |
| issn | 1878-7479 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurotherapeutics |
| spelling | doaj-art-7e42b1ac2aa24c0ca9389a97c500294e2025-08-20T03:38:22ZengElsevierNeurotherapeutics1878-74792025-07-01224e0058110.1016/j.neurot.2025.e00581Intranasal insulin for improving cognitive function in multiple sclerosisScott D. Newsome0Kathryn C. Fitzgerald1Abbey Hughes2Meghan Beier3Jacqueline Koshorek4Yujie Wang5Daniela Pimentel Maldonado6Thomas Shoemaker7Taimur Malik8Tarik Bayu9Pablo E. Ravenna10Ama Avornu11Elias S. Sotirchos12Meghan Romba13John Muschelli14Todd T. Brown15Peter A. Calabresi16Ellen M. Mowry17Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USA; Corresponding author.Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USAJohns Hopkins University School of Medicine, Division of Rehabilitation Psychology and Neuropsychology, Baltimore, MD, USAJohns Hopkins University School of Medicine, Division of Rehabilitation Psychology and Neuropsychology, Baltimore, MD, USAJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USAJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USAJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USAJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USAJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USAJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USAJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USAJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USAJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USAJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USAJohns Hopkins Bloomberg School of Public Health, Department of Biostatistics, Baltimore, MD, USAJohns Hopkins University School of Medicine, Division of Endocrinology, Baltimore, MD, USAJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USAJohns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, USACognitive impairment is common in people with multiple sclerosis (PwMS). There is an urgent need to identify/develop novel therapies that can help cognitive function in MS. Insulin is critical for helping with regulation of multiple CNS functions, including learning and memory. Insulin administrated intranasally has shown to improve memory and learning in healthy people and in those with some neurodegenerative disorders. Hence, there was rationale for investigating intranasal insulin in PwMS who experience cognitive impairment. We completed a phase Ib/II, randomized, double-blind, placebo-controlled trial; participants were randomized in a 1:1:1 fashion, stratified by relapsing versus progressive MS, to intranasal insulin 10 international units (IU) twice a day, 20 IU twice a day, or placebo for 24 weeks. One-hundred and five PwMS were enrolled, 69 of whom had at least one follow up visit during the active treatment phase of the trial (baseline to week 24). The cohort's mean age was 52.4 ± 9.7years, 62 % were female, and ∼60 % had relapsing-remitting MS. The most common side effects amongst treatment groups included headache, rhinorrhea, and dizziness. There were 13 SAEs which were not deemed study drug related; there were no deaths. The main clinical outcome measure, SDMT, did not demonstrate any difference between intranasal insulin and placebo. Similar findings were noted for all secondary outcome measures. Intranasal insulin appeared safe and well-tolerated in PwMS. However, it was not superior to placebo in any of the clinical outcome measures assessed, which could have been impacted by the duration of the trial, small sample size for a three-arm trial design, data missingness (particularly during COVID-19), outcome measure insensitivity to change, baseline cognitive reserve, or other factors. Nonetheless, intranasally-administered therapeutics may be of interest to develop further as a way to get across the blood brain barrier.http://www.sciencedirect.com/science/article/pii/S1878747925000595Multiple sclerosisCognitive dysfunctionInsulinClinical trialsIntranasal treatments |
| spellingShingle | Scott D. Newsome Kathryn C. Fitzgerald Abbey Hughes Meghan Beier Jacqueline Koshorek Yujie Wang Daniela Pimentel Maldonado Thomas Shoemaker Taimur Malik Tarik Bayu Pablo E. Ravenna Ama Avornu Elias S. Sotirchos Meghan Romba John Muschelli Todd T. Brown Peter A. Calabresi Ellen M. Mowry Intranasal insulin for improving cognitive function in multiple sclerosis Neurotherapeutics Multiple sclerosis Cognitive dysfunction Insulin Clinical trials Intranasal treatments |
| title | Intranasal insulin for improving cognitive function in multiple sclerosis |
| title_full | Intranasal insulin for improving cognitive function in multiple sclerosis |
| title_fullStr | Intranasal insulin for improving cognitive function in multiple sclerosis |
| title_full_unstemmed | Intranasal insulin for improving cognitive function in multiple sclerosis |
| title_short | Intranasal insulin for improving cognitive function in multiple sclerosis |
| title_sort | intranasal insulin for improving cognitive function in multiple sclerosis |
| topic | Multiple sclerosis Cognitive dysfunction Insulin Clinical trials Intranasal treatments |
| url | http://www.sciencedirect.com/science/article/pii/S1878747925000595 |
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