Ralf Ludwig: Targeting Neutrophil-Driven Autoimmunity Through CDK Inhibition
Ralf Ludwig, Director of the Lübeck Institute of Experimental Dermatology at the University of Lübeck, shared a post on LinkedIn:
“Twenty-two authors, seven institutions, three countries. One name at the front.
Mareile Schlotfeldt is a doctoral researcher in our DFG-funded Research Training Group 2633, ‘Defining and Targeting Autoimmune Pre-Disease’.
She is first and corresponding author of our paper on CDK inhibition in neutrophil-driven autoimmunity, now out in Cell Communication and Signaling.
The work runs the full distance from human cell to mouse model:
- which CDKs a neutrophil still expresses, although it will never divide again
- 14 CDK inhibitors tested against five neutrophil functions
- the strongest taken into experimental epidermolysis bullosa acquisita, systemically and topically
- the lead compound then tested in arthritis, where it worked, and in immune thrombocytopenia, where neutrophils are not central and it did nothing
The paper’s own contributions statement lists her for investigation, formal analysis, visualisation and the original draft. The colleagues alongside her sat in Luebeck, Erlangen, Chicago, Amsterdam, Utrecht, Borstel and Marburg.
She is also first author of a second, larger kinase screen in neutrophils. That one is a preprint and has not yet been peer-reviewed.
For anyone in drug development, the reusable part is not the CDKs.
It is the route: human neutrophil assays that read five effector functions, then antibody-transfer models in skin and joint, with a model in which neutrophils are not central, to show when a compound should not work.
If you have a compound aimed at the effector phase of antibody-mediated disease, that route is available. Talk to us.”
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