Noonan Syndrome

Noonan syndrome (NS) is a rare disorder that is typically diagnosed at birth. It affects the child’s development resulting in stunted growth, abnormal facial features, and heart defects, such as hypertrophic cardiomyopathy (HCM).

Noonan syndrome is caused by mutations to the PTPN11, SOS1 RIT1, KRAS, or RAF1 genes. NS belongs to a group of diseases called RASopathies. RASopathies are all caused by the mutation of proteins that belong to the Ras family and the mitogen-activated protein kinase family.

Unfortunately, researchers have yet to find a way to repair the mutated gene that causes NS. Treatment instead focuses on controlling symptoms on a case to case basis. These include medication, surgery, and even a heart transplant.

NS can be life-threatening, especially when it leads to heart disease.

Infants who are diagnosed with NS, HCM as well as congestive heart failure have a 1 year survival rate of 34%.

However, researchers at CHU Sainte-Justine Research Center and the Université de Montréal have just released results from a new study which were so positive that the team now believes NS may actually be treatable.

Exciting Results

The team investigated a drug called trametinib, which is a MEK inhibitor. This is the first time that researchers have investigated a treatment which specifically targets the resulting processes that stem from the mutations that cause RASopathies.

Trametinib was tested in two RIT1-associated NS patients. Here are the results.

• After 3 months, the cardiac status and overall clinical status of the patients was drastically improved.
• Vascular obstruction and HCM was reversed.
• Hypertrophy decreased and this improvement was sustained during 17 months of trametinib treatment.
• Laboratory values were normalized.
• One of the two patients who had required ventilation was able to be extubated after just 6 weeks of the therapy.
• Overall growth was improved.

The fact that both patients were not only able to be stabilized with the treatment but both also had their heart disease reverse has made researchers extremely hopeful about the potential of this therapy.

These full results have been published in the Journal of American College of Cardiology.

Need For Larger Study

Unfortunately, because this investigation was so small, larger trials utilizing more patients are necessary to confirm this treatments safety and efficacy.

That said, this small study has led the way for further research of MEK inhibition not just in NS, but as a potential therapy for other RASopathies as well.

Researchers now want to investigate the optimal dosing of trametinib in NS, its long-term side effects, and the optimal treatment window for patients. The research team believes that MEK inhibition may actually be most effective during a very specific window of time, before irreversible cardiac remodeling takes place.

Ultimately, much more research is needed into this potential treatment for NS, but the initial results from these two patients is extremely promising for this rare condition that has yet to have a cure.

You can read more about this investigation and the next steps for this potential therapy here.