New approach to treat patients suffering from Noonan-Syndrome

A new therapeutic approach shows promise for treating the most clinically severe Noonan Syndrome (NS) manifestation. A small molecule drug candidate, which specifically blocks a single receptor, reduces disease specific markers in a  Noonan-Model System.

Challenge

Noonan Syndrome is a mutli-genetic disorder (1:1,000–1:2,500 births). Currently only some of the symptoms can be treated, since there is no effective therapeutic approach to treat the disease itself. Many symptoms cannot be treated like facial deformations, malformed bones or a short statue, but also bleeding disorders or heart problems occur. Up to 35% of NS patients develop a Hypertrophic CardioMyopathy (HCM), significantly increasing the risk of heart failure and early mortality. A tailored therapy against Noonan-Induced HCM is not available, but highly needed.

Our Solution

A team of researchers at the University Medical Center in Göttingen, has identified a potential target to treat patients suffering from Noonan-Syndrome. The inhibition of a specific receptor with Substance A in cells of a Noonan disease model cell line significantly reduces Noonan specific markers. A similar effect was not observed in control cells. This renders it possible, that the therapeutic approach specifically compensates metabolic defects caused by Noonan-Syndrome mutations.

Figure 1: Top: Engineered cardiac tissues (ETCs), grown from  wildtype and Noonan-disease model cells. Bottom: Analysis of pole deflection (left) and Young’s modules (right). Both cells-types were treated with 10 µM of Substance A. The pole deflection and also the Youngs modules could normalize both symptoms to nearly wildtype levels.

It was found that treatment with Subst-A ameliorates the Noonan-disease-model associated disease phenotype. Importantly, this effect was observed across multiple NS genotypes, indicating a broad therapeutic relevance.

This data points to a function of Substance A, that compensates the effect of Noonans Disease on a cellular level. Thus a treatment of the cause of the disease and not only of the symptoms might be possible. Data for pharmakokinetics and toxicity are available, thus a fast track for an orphan designation might be possible.

Advantages

•  Very high rare disease prevalence: 1:1.000 to 1:2.500 births (classified as a rare/orphan disease).
• High economic potential due to:
  • high-value orphan drug opportunity with long-term market relevance
  • cearly defined patient subgroup (genetically)
  • fast track for an orphan disease might be possible

Applications

• Acute and preventive treatment of Noonan-Syndrome Patients

Development Status

A Noonan-Syndrome specific disease phenotype was eliminated in cell culture and organoids.

Patent Status

A priority patent application has been filed in the name of the University Medical Center of Göttingen. Worldwide IP-rights possible, a licensing or collaboration partner is sought.

Contact

Dr.Martin Andresen
Patent Manager Life Sciences
E-Mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
Tel.: +49 551 30724 150
Reference: BioT-2570-UMG

Tags: orphan, rare disease, RASopathie, Noonan Syndrome