CiMUS - USC researchers advance in the potential application of drugs to reverse excessive bleeding in patients with Noonan Syndrome.

• Noonan syndrome is a congenital disease that can cause, among other health problems, excessive bleeding due to coagulation defects or a lack of platelets.
• The CiMUS group led by Ángel García discovers a drug that inhibits the SHP2 enzyme and improves platelet function.
• The research, which was done in collaboration with the University of Maastricht and was the topic of a PhD thesis, has just been published in the journal Thrombosis Research.

Noonan syndrome is a congenital disease that prevents the normal development of various parts of the body. Patients have a characteristic facial appearance that is more pronounced in infants and children. Approximately 40% of those affected have bleeding problems, mostly due to platelet dysfunction and abnormalities in blood clotting. These problems include gene mutation resulting in increased activity of SHP2 phosphatase, a type of enzyme known to promote tumour cell survival. SHP2 phosphatase negatively regulates platelet activation mediated by the collagen receptor GPVI, so increased SHP2 activity leads to increased platelet inhibition and subsequent bleeding problems.

Now, a study by the CiMUS group Platelet Proteomics and IDIS led by Ángel García has just shown that the treatment of Noonan syndrome patients' platelets with an SHP2 inhibitor drug (called SHP099, which is currently undergoing clinical trials as an antitumoural) partially reverses these patients' bleeding issues by improving platelet function.

Clinical variability and challenging diagnosis

Noonan syndrome is a relatively common genetic disease that causes short stature, slowed growth, congenital heart disease and a characteristic facial phenotype.

Signs and symptoms of Noonan syndrome can range from moderate to severe and are highly variable from person to person. They also include musculoskeletal problems, learning difficulties, eye and hearing diseases, lymphatic disorders, genital and renal ailments or skin diseases.

Diagnosis is primarily clinical and can be difficult to establish with certainty, especially in adults. There is great variability in clinical manifestations and the phenotype becomes less evident with age.

This work has been carried out in collaboration with the University of Maastricht and has been funded by a European project shared between Maastricht and USC. The results have just been published in the prestigious journal "Thrombosis Research" and have been part of the doctoral thesis of Delia I. Fernández de la Fuente, recently defended as part of a European PhD Programme focused on the search for new antithrombotics, coordinated at the USC by Ángel García.

Link to the publication: Role of SHP2 (PTPN11) in glycoprotein VI-dependent thrombus formation: Improved platelet responsiveness by the allosteric drug SHP099 in Noonan syndrome patients - PubMed (nih.gov)