According to researchers at Université de Montréal and CHU Sainte-Justine Research Center, Canada, there may be a new Noonan syndrome treatment on the horizon.
Noonan Syndrome (NS) is a rare genetic syndrome typically evident at birth that prevents normal development in various parts of the body and often linked to early-onset severe heart disease. NS is part of a group of diseases termed RASopathies that are caused by activating mutations of proteins belonging to the Ras and mitogen-activated protein kinase families. The new therapeutic option brings infants promising Noonan syndrome treatment.
Noonan syndrome treatment
Published in the Journal of the American College of Cardiology, researchers show that a MEK inhibitor called trametinib can reverse hypertrophic cardiomyopathy (HCM) and valvular obstruction in patients with RIT1-associated NS.
”Up to this finding, our therapeutic options were limited to surgery, including heart transplant, and symptomatic relief with medication,” said study author Dr. Gregor Andelfinger, a paediatric cardiologist at CHU Sainte-Justine, a researcher at Sainte-Justine University Hospital Research Center in the fetomaternal and neonatal pathologies axis, and an associate research professor in the paediatrics department of Université de Montréal.
“Trametinib treatment is the first approach specifically targeted to the molecular cause of RASopathies,” adds Andelfinger.
“While our numbers are still very limited, we report the first patients in whom we were not only able to stabilise, but to reverse the disease of the heart. These results pave the way for larger trials, which are now needed.”
Sustained improvement shown
Infants less than six months old with Noonan syndrome, hypertrophic cardiomyopathy and congestive heart failure normally have a poor prognosis, with a one-year survival rate of 34%. In the new study, the Sainte Justine clinical teams used trametinib, an inhibitor targeted specifically against the activating nature of the mutations, to try to treat NS in two patients.
They observed dramatic improvement of clinical and cardiac status in the patients only three months after treatment. Hypertrophy regressed in both patients, with sustained improvement over a total of 17 months of treatment, and normalisation of laboratory values.
One of the patients, who required ventilation, could be extubated after six weeks of treatment. Both patients showed better overall growth after treatment was started.
Can researchers treat the untreatable?
“The findings described in this report suggest that a life-threatening form of heart disease affecting young infants might be treatable, which, if true, would be unprecedented and so meaningful for the families whose lives this devastating problem touches,” commented Dr. Bruce Gelb, Director of the Mindich Child Health and Development Institute, Icahn School of Medicine, USA.
“Now we need to perform a proper clinical trial to prove that this drug is definitely working for this particular problem,” he concluded.
