A cancer drug effective against serious heart problems 💖

Could a drug already available for cancer be used to treat some children with Noonan syndrome? This is what a retrospective study conducted by a large international research partnership involving 27 institutions suggests.


In this study, the research team analyzed the clinical records of 61 children suffering from thickening of the heart muscle, one of the manifestations of Noonan syndrome. They were admitted between 2000 and 2023 to one of the 23 participating hospitals (10 countries). About half of the patients received the usual treatment, while the others also received compassionate treatment with trametinib.

This drug, initially developed for cancer treatment, inhibits the MEK protein, which is overactivated in the cells of children with Noonan syndrome. It is this overactivation that causes pathological thickening of the heart walls.

Result: over three years, children who were prescribed the usual treatment alone had an 80% chance of undergoing surgery, heart transplantation, or dying. These probabilities dropped to 20% for children whose usual treatment was supplemented with trametinib.

"This is a major difference," says Dr. Andelfinger. "Currently, no treatment addresses the root cause of the problem, which is the overactivation of a protein in the heart muscle cells. Our study provides, for the first time, a very strong signal of efficacy in a statistically significant group of subjects."

Towards a clinical trial

In a smaller-scale study published in 2019, Dr. Andelfinger and his colleagues observed similar positive effects of trametinib in two babies with hypertrophic cardiomyopathy due to Noonan syndrome.

The retrospective study published today provides additional evidence, suggesting the potential of this treatment to prevent heart complications in babies with Noonan syndrome or other similar diseases. This is why the research team is working on setting up an international clinical trial that could demonstrate its efficacy in various situations, including specific cases.

"Some children did not respond to the compassionate treatment with trametinib, for reasons that remain to be validated," explains Dr. Andelfinger. "Nevertheless, our preliminary data seem to indicate that this treatment could ultimately allow us to improve the prognosis for the vast majority of our patients."

About Noonan syndrome

Noonan syndrome is a rare disease caused by a genetic mutation, characterized by delayed development of several parts of the body, leading, among other things, to short stature and distinctive facial features. It can lead to several complications, particularly in the heart.

Approximately 1 in 2500 children carries this mutation, and of these, 1 in 5 develops hypertrophic cardiomyopathy. This condition causes the death of more than half of the affected babies before the age of one. Currently available treatments aim to alleviate the symptoms of the disease and manage its complications.

The research team

The results are published by a group of researchers from several countries, including Dr. Cordula Wolf from the University of Munich, Dr. Martin Zenker from the University of Magdeburg, Dr. Bruce D. Gelb from the Mount Sinai School of Medicine, and Dr. Gregor Andelfinger, a professor in the Department of Pediatrics at the University of Montreal and a clinician-researcher at CHU Sainte-Justine.