A Novel Target for Treatment of Rare Genetic Diseases Caused by Nonsense Mutations

Karni Rotem, HUJI, School of Medicine - IMRIC, Biochemistry and Molecular Biology


A nonsense mutation is an alteration in the genetic code that prematurely halts the synthesis of an essential protein, such as dystrophin in Duchenne muscular dystrophy. Nonsense mutations caused by premature stop codon, are treated using read-through therapies that are only partially efficient since they rely on the existence of mutant mRNA which is unstable.

Our Innovation

The proposed invention is a novel target for the treatment of genetic diseases caused by nonsense mutations, which increases the success of current read through therapies, and may serve as a stand-alone treatment in cases that premature stop codon is not involved but the mRNA is unstable for other reasons.


  • Novel target with several proposed small molecules to inhibit this target (repositioning of existing drugs).
  • since the compounds are small molecules, they are stable, dosage-regulated, and have increased penetration to all body tissues – advantage in Duchenne delivery to muscles, and CF delivery to the lungs.
  • In-vitro results using cells derived from Duchene and Becker patients show increased mRNA stability.

The Opportunity

  • Nonsense mutation are the cause of many genetic diseases, such as Duchenne/Becker, Cystic fibrosis and others. Despite rapid developments over the last years, there remains a large unmet need among patients who are not amenable to mutation-specific drugs.
  • Duchenne, Becker and CF are rare diseases and considered orphan diseases by the FDA with an accelerated regulatory path.
  • Existing read-through drugs have poor effectiveness. The technology suggests  increased effectiveness and relief of Duchenne symptoms.
  • This technology is applicable for other genes and not limited to Dystrophin (Becker and Duchenne target) or CFTR (Cystic fibrosis).
  • The team has the capabilities to advance the technology up to pre-clinical studies.

 Development Milestones

Preliminary results to support the core of the invention were obtained in patient-derived cells.

Next steps are in-vivo studies

Figure 1. A general scheme of nonsense mutation causing mRNA degradation and mRNA stabilization by targeted drugs.




Contact for more information:

Mel Larrosa
VP Business Development Healthcare
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