Part of the research published in Circulation was carried out in the US in collaboration with Dr. Lutz Tautz’s team, at the Sanford Burnham Medical Research Institute (SBMRI) of La Jolla, California, where Souad Rahmouni performed her post-doctoral training on the family of protein phosphatases. SBMRI has an important molecular screening center (Conrad Prebys Center for Chemical Genomics) with an industrial capability of drug screening where it is possible to find a needle in a haystack. In this case, the objective was to identify a synthetic molecule among hundreds of thousands that would behave as a “blocking agent” for the enzymatic activity of DUSP3 protein. In other words, a molecule that will bind DUSP3 and prevent it from carrying out its function. The screening performed at Sanford-Burnham Institute was conducted by powerful robots and analyzed more than 300,000 molecules !

Thanks to this screening, Dr. Tautz’s team isolated about ten inhibitory molecules specific to DUSP3 protein. These molecules were tested in Liège on isolated platelets from human blood (tests carried out ex vivo) in order to verify their impact on platelet activation and aggregation. The dialogue between Liège and La Jolla lasted for nearly two years and resulted in the design of a molecule that reproduced the same effect as the genetic suppression of the DUSP3 protein in mice, i.e., an inhibition of platelet activity. Specificity studies against other members of the phosphatases family were performed and showed that the selected molecule was highly specific to DUSP3. Perspectives are the study of toxicity of this new molecule in mice, which is ongoing at the Sanford-Burnham Institute.

If this study proves to be conclusive, the scientists will verify the efficacy of the molecule in vivo in mice. As in the case of the Knock Out mice, it will be necessary to measure the impact on platelet activity as well as resistance to thrombosis in treated as compared to untreated mice.  

Clinical research on humans can only begin if results on animals prove to be conclusive. An eventual treatment against blood clots may be at the end of this road but many years down the line.