glunomab

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glunomab

GtoPdb Ligand ID: 13183

Synonyms: glunozumab

Comment: Glunomab is a mouse monoclonal antibody that is designed to block tissue-type plasminogen activator (tPA)-mediated potentiation of N-methyl-D-aspartate (NMDA) glutamate receptor function in neuroendothelial cells [2]. The antibody targets a regulatory site within the N-terminal domain of the human GluN1 (GRIN1) subunit of NMDA receptors, and prevents tPA binding. This mechanism is proposed to reduced tPA-mediated immune cell transmigration across the blood-brain barrier and is expected to counteract neuroinflammatory damage that is observed in neurological diseases such as multiple sclerosis, Parkinson's disease and stroke [1,3].
Lys Therapeutics' clinical lead LYS241 with this mechanism of action is a humanised and matured version of glunomab.

References
1. Lebrun F, Levard D, Lemarchand E, Yetim M, Furon J, Potzeha F, Marie P, Lesept F, Blanc M, Haelewyn B et al.. (2024) Improving stroke outcomes in hyperglycemic mice by modulating tPA/NMDAR signaling to reduce inflammation and hemorrhages. Blood Adv, 8 (5): 1330-1344. [PMID:38190586]
2. Lesept F, Chevilley A, Jezequel J, Ladépêche L, Macrez R, Aimable M, Lenoir S, Bertrand T, Rubrecht L, Galea P et al.. (2016) Tissue-type plasminogen activator controls neuronal death by raising surface dynamics of extrasynaptic NMDA receptors. Cell Death Dis, 7 (11): e2466. [PMID:27831563]
3. Macrez R, Ortega MC, Bardou I, Mehra A, Fournier A, Van der Pol SM, Haelewyn B, Maubert E, Lesept F, Chevilley A et al.. (2016) Neuroendothelial NMDA receptors as therapeutic targets in experimental autoimmune encephalomyelitis. Brain, 139 (Pt 9): 2406-19. [PMID:27435092]

References

1. Lebrun F, Levard D, Lemarchand E, Yetim M, Furon J, Potzeha F, Marie P, Lesept F, Blanc M, Haelewyn B et al.. (2024)
Improving stroke outcomes in hyperglycemic mice by modulating tPA/NMDAR signaling to reduce inflammation and hemorrhages.
Blood Adv, 8 (5): 1330-1344. [PMID:38190586]

2. Lesept F, Chevilley A, Jezequel J, Ladépêche L, Macrez R, Aimable M, Lenoir S, Bertrand T, Rubrecht L, Galea P et al.. (2016)
Tissue-type plasminogen activator controls neuronal death by raising surface dynamics of extrasynaptic NMDA receptors.
Cell Death Dis, 7 (11): e2466. [PMID:27831563]

3. Macrez R, Ortega MC, Bardou I, Mehra A, Fournier A, Van der Pol SM, Haelewyn B, Maubert E, Lesept F, Chevilley A et al.. (2016)
Neuroendothelial NMDA receptors as therapeutic targets in experimental autoimmune encephalomyelitis.
Brain, 139 (Pt 9): 2406-19. [PMID:27435092]