ArticleFluids and barriers of the CNS2022
Exploring ITM2A as a new potential target for brain delivery.
Article in Fluids and barriers of the CNS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Decoding the senescent endothelial landscape in ischemic stroke through single-cell and bulk RNA sequencing.Functional & integrative genomics · 2026Article
- The emerging roles of ITM2A: At the molecular crossroads of development and pathogenesis.iScience · 2026Review
- Obesity drives depot-specific vascular remodeling in male white adipose tissue.Nature communications · 2025Article
- Direct interoceptive input to the insular cortex shapes learned feeding behavior.bioRxiv : the preprint server for biology · 2025Article
- Exploring the Role of Inflammation and Metabolites in Bell's Palsy and Potential Treatment Strategies.Biomedicines · 2025Article
- Identification of Cell Fate Determining Transcription Factors for Generating Brain Endothelial Cells.Stem cell reviews and reports · 2025Article
- Multi-omics identification and validation of oxidative phosphorylation-related hub genes in schizophrenia.Frontiers in genetics · 2025Article
- Functional and Biological Characterization of the LGR5Δ5 Splice Variant in HEK293T Cells.International journal of molecular sciences · 2024Article
- An easy-to-perform method for microvessel isolation and primary brain endothelial cell culture to study Alzheimer's disease.Heliyon · 2024Article
- Acute severe hypoglycemia alters mouse brain microvascular proteome.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Receptor-mediated transcytosis for brain delivery of therapeutics: receptor classes and criteria.Frontiers in drug delivery · 2024Review
- Three-dimensional morphologic and molecular atlases of nasal vasculature.Nature cardiovascular research · 2023Article
- Post-ischemic inflammatory response in the brain: Targeting immune cell in ischemic stroke therapy.Frontiers in molecular neuroscience · 2023Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIntegral membrane protein 2A (ITM2A) is a transmembrane protein expressed in a variety of tissues; little is known about its function, particularly in the brain. ITM2A was found to be highly enriched in human brain versus peripheral endothelial cells by transcriptomic and proteomic studies conducted within the European Collaboration on the Optimization of Macromolecular Pharmaceutical (COMPACT) Innovative Medicines Initiative (IMI) consortium. Here, we report the work that was undertaken to determine whether ITM2A could represent a potential target for delivering drugs to the brain.
methodsA series of ITM2A constructs, cell lines and specific anti-human and mouse ITM2A antibodies were generated. Binding and internalization studies in Human Embryonic Kidney 293 (HEK293) cells overexpressing ITM2A and in brain microvascular endothelial cells from mouse and non-human primate (NHP) were performed with these tools. The best ITM2A antibody was evaluated in an in vitro human blood brain barrier (BBB) model and in an in vivo mouse pharmacokinetic study to investigate its ability to cross the BBB.
resultsAntibodies specifically recognizing extracellular parts of ITM2A or tags inserted in its extracellular domain showed selective binding and uptake in ITM2A-overexpressing cells. However, despite high RNA expression in mouse and human microvessels, the ITM2A protein was rapidly downregulated when endothelial cells were grown in culture, probably explaining why transcytosis could not be observed in vitro. An attempt to directly demonstrate in vivo transcytosis in mice was inconclusive, using either a cross-reactive anti-ITM2A antibody or in vivo phage panning of an anti-ITM2A phage library.
conclusionsThe present work describes our efforts to explore the potential of ITM2A as a target mediating transcytosis through the BBB, and highlights the multiple challenges linked to the identification of new brain delivery targets. Our data provide evidence that antibodies against ITM2A are internalized in ITM2A-overexpressing HEK293 cells, and that ITM2A is expressed in brain microvessels, but further investigations will be needed to demonstrate that ITM2A is a potential target for brain delivery.
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