MONTRÉAL, JANUARY 8, 2025 – Could a cancer drug already on the market be used to treat certain children with Noonan syndrome (NS)? A new retrospective study conducted by a vast international research partnership of 27 institutions suggests that this is the case. The findings were published today by an international group of researchers, including Dr. Cordula Wolf of the Technical University of Munich, Dr. Martin Zenker of the University of Magdeburg, Dr. Bruce D. Gelb of Mount Sinai University and Dr. Gregor Andelfinger, clinician-researcher at CHU Sainte-Justine.

The study analyzed the clinical records of 61 NS patients with thickening of the heart muscle. These patients were admitted to one of the 23 participating hospitals (10 countries) between 2000 and 2023. About half the patients received standard treatment, while the other comparable half also received compassionate use of trametinib. First developed as a cancer treatment, this drug inhibits the MEK protein, which is over-activated in the cells of children with NS, causing pathological thickening of the heart wall.

The findings show that, over a three-year period, children who received the standard treatment alone had an 80% probability of undergoing surgery, a heart transplant or dying. The probability fell to 20% for children who were also treated with trametinib. “That makes a big difference,” said Dr. Andelfinger, who is also a full professor in the Department of Pediatrics at Université de Montréal. “There’s no treatment available right now that targets the root of the problem, which is the hyperactivation of a protein in heart muscle cells. For the first time, our study has provided a very strong efficacy signal in a statistically significant treatment group.” 

Towards a clinical trial

In an earlier, smaller study published in 2019, Dr. Andelfinger and his colleagues had already observed similar positive effects of trametinib in two babies with NS-associated hypertrophic cardiomyopathy. The retrospective study published today provides further evidence that this treatment has the potential to prevent cardiac complications in babies with NS or similar conditions. Researchers are now working to set up an international clinical trial to demonstrate its efficacy across a broad spectrum and in specific cases.

“Some children didn’t respond to the compassionate use of trametinib for reasons that have yet to be determined,” said Dr. Andelfinger. “Nevertheless, the preliminary data published today suggest that this treatment could eventually allow us to improve the prognosis for the vast majority of our patients.” 

About Noonan syndrome

NS is a rare disease caused by a genetic mutation characterized by slowed development of several body parts, leading to short stature and peculiar facial features. Various complications can arise, particularly heart-related. Around one child in 2,500 is thought to carry the mutation, and of these, one in five will develop hypertrophic cardiomyopathy. This heart complication leads to the death of more than half of all affected babies before the age of one. Currently available treatments are aimed at alleviating symptoms and managing complications.