Mechanisms of Intranasal Deferoxamine in Neurodegenerative and Neurovascular Disease
Identifying disease-modifying therapies for neurological diseases remains one of the greatest gaps in modern medicine. Herein, we present the rationale for intranasal (IN) delivery of deferoxamine (DFO), a high-affinity iron chelator, as a treatment for neurodegenerative and neurovascular disease wi...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/2/95 |
| _version_ | 1827597606021234688 |
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| author | Jacob Kosyakovsky Jared M. Fine William H. Frey Leah R. Hanson |
| author_facet | Jacob Kosyakovsky Jared M. Fine William H. Frey Leah R. Hanson |
| author_sort | Jacob Kosyakovsky |
| collection | DOAJ |
| description | Identifying disease-modifying therapies for neurological diseases remains one of the greatest gaps in modern medicine. Herein, we present the rationale for intranasal (IN) delivery of deferoxamine (DFO), a high-affinity iron chelator, as a treatment for neurodegenerative and neurovascular disease with a focus on its novel mechanisms. Brain iron dyshomeostasis with iron accumulation is a known feature of brain aging and is implicated in the pathogenesis of a number of neurological diseases. A substantial body of preclinical evidence and early clinical data has demonstrated that IN DFO and other iron chelators have strong disease-modifying impacts in Alzheimer’s disease (AD), Parkinson’s disease (PD), ischemic stroke, and intracranial hemorrhage (ICH). Acting by the disease-nonspecific pathway of iron chelation, DFO targets each of these complex diseases via multifactorial mechanisms. Accumulating lines of evidence suggest further mechanisms by which IN DFO may also be beneficial in cognitive aging, multiple sclerosis, traumatic brain injury, other neurodegenerative diseases, and vascular dementia. Considering its known safety profile, targeted delivery method, robust preclinical efficacy, multiple mechanisms, and potential applicability across many neurological diseases, the case for further development of IN DFO is considerable. |
| first_indexed | 2024-03-09T03:33:45Z |
| format | Article |
| id | doaj.art-a26d39a7966e4d1ca7cac70db418906b |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T03:33:45Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-a26d39a7966e4d1ca7cac70db418906b2023-12-03T14:51:43ZengMDPI AGPharmaceuticals1424-82472021-01-011429510.3390/ph14020095Mechanisms of Intranasal Deferoxamine in Neurodegenerative and Neurovascular DiseaseJacob Kosyakovsky0Jared M. Fine1William H. Frey2Leah R. Hanson3School of Medicine, University of Virginia, 200 Jeanette Lancaster Way, Charlottesville, VA 22903, USAHealthPartners Neuroscience Center, HealthPartners Institute, Saint Paul, MN 55130, USAHealthPartners Neuroscience Center, HealthPartners Institute, Saint Paul, MN 55130, USAHealthPartners Neuroscience Center, HealthPartners Institute, Saint Paul, MN 55130, USAIdentifying disease-modifying therapies for neurological diseases remains one of the greatest gaps in modern medicine. Herein, we present the rationale for intranasal (IN) delivery of deferoxamine (DFO), a high-affinity iron chelator, as a treatment for neurodegenerative and neurovascular disease with a focus on its novel mechanisms. Brain iron dyshomeostasis with iron accumulation is a known feature of brain aging and is implicated in the pathogenesis of a number of neurological diseases. A substantial body of preclinical evidence and early clinical data has demonstrated that IN DFO and other iron chelators have strong disease-modifying impacts in Alzheimer’s disease (AD), Parkinson’s disease (PD), ischemic stroke, and intracranial hemorrhage (ICH). Acting by the disease-nonspecific pathway of iron chelation, DFO targets each of these complex diseases via multifactorial mechanisms. Accumulating lines of evidence suggest further mechanisms by which IN DFO may also be beneficial in cognitive aging, multiple sclerosis, traumatic brain injury, other neurodegenerative diseases, and vascular dementia. Considering its known safety profile, targeted delivery method, robust preclinical efficacy, multiple mechanisms, and potential applicability across many neurological diseases, the case for further development of IN DFO is considerable.https://www.mdpi.com/1424-8247/14/2/95intranasaldeferoxamineAlzheimer’s diseaseParkinson’s diseaseischemic strokeintracranial hemorrhage |
| spellingShingle | Jacob Kosyakovsky Jared M. Fine William H. Frey Leah R. Hanson Mechanisms of Intranasal Deferoxamine in Neurodegenerative and Neurovascular Disease Pharmaceuticals intranasal deferoxamine Alzheimer’s disease Parkinson’s disease ischemic stroke intracranial hemorrhage |
| title | Mechanisms of Intranasal Deferoxamine in Neurodegenerative and Neurovascular Disease |
| title_full | Mechanisms of Intranasal Deferoxamine in Neurodegenerative and Neurovascular Disease |
| title_fullStr | Mechanisms of Intranasal Deferoxamine in Neurodegenerative and Neurovascular Disease |
| title_full_unstemmed | Mechanisms of Intranasal Deferoxamine in Neurodegenerative and Neurovascular Disease |
| title_short | Mechanisms of Intranasal Deferoxamine in Neurodegenerative and Neurovascular Disease |
| title_sort | mechanisms of intranasal deferoxamine in neurodegenerative and neurovascular disease |
| topic | intranasal deferoxamine Alzheimer’s disease Parkinson’s disease ischemic stroke intracranial hemorrhage |
| url | https://www.mdpi.com/1424-8247/14/2/95 |
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