Atherosclerosis, the underlying cause of the majority of cardiovascular diseases, is a lipid driven, inflammatory disease of
the large arteries. Despite a 25% relative risk reduction achieved by lipid-lowering treatment, the vast majority of
atherosclerosis induced cardiovascular disease risk remains unaddressed. Therefore, characterizing mediators of the
inflammatory aspect of atherosclerosis is a widely recognized scientific goal with great therapeutic implications. Blocking the
co-stimulatory CD40L-CD40 dyad reduces atherosclerosis. However, long-term inhibition of CD40L or its receptor CD40
results in suppression of the immune system and poses a risk for thromboembolic events. Therefore, we focused on the
downstream signaling pathways of CD40, and found that the interaction between CD40 and TNF-receptor-associated factor
6 (TRAF6) is the driving force for atherosclerosis. Using virtual ligand screening, we identified several small molecule
inhibitors termed TRAF-STOPs that were modeled to bind to the CD40-binding domain of TRAF6. TRAF-STOPs significantly
reduce (existing) atherosclerosis and treatment was well tolerated. The first toxicology results in mice show that there are no
side effects. Here we pursue the hypothesis that TRAF-STOPs are excellent candidates to pass the translational pipeline
towards a clinical application to treat atherosclerotic cardiovascular disease. Prof. Lutgens is one of the founders of the
recently established start-up company Cartesio Therapeutics to be able to valorise our novel TRAF-STOPs. By the end of
the PoC grant, we expect to have an oral drug available and to have completed toxicology and bio-distribution analysis in a
large animal model (mini-pig) and have tested TRAF-STOPs in a pig model of atherosclerosis. This way, we hold a solid
business case in our hands. The resulting business- and (pre-)clinical development plan and patent portfolio will then be
ready for seed investment and venture capital funding.
Are you the coordinator (or a participant) of this project? Plaese send me more information about the "TRACER" project.
For instance: the website url (it has not provided by EU-opendata yet), the logo, a more detailed description of the project (in plain text as a rtf file or a word file), some pictures (as picture files, not embedded into any word file), twitter account, linkedin page, etc.
Send me an email (fabio@fabiodisconzi.com) and I put them in your project's page as son as possible.
Thanks. And then put a link of this page into your project's website.
The information about "TRACER" are provided by the European Opendata Portal: CORDIS opendata.
More projects from the same programme (H2020-EU.1.1.)
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