LLPS interference-based molecular therapeutics for NEDAMSS syndrome

The recently identified neurodevelopmental syndrome NEDAMSS, which has no available cure, is caused by mutations in one of the two copies of the IRF2BPL gene. The mutant copy of the gene produces a non-functional protein that localizes in clumps outside the cell nucleus which entrap the functional IRF2BPL protein produced by the normal copy of the gene. The lack of normal IRF2BPL protein in the nucleus of brain cells is a key mechanism triggering the disease. This project will develop novel strategies to interfere with this key pathological mechanism, providing proof-of-concept pre-clinical evidence of the feasibility and efficacy of a novel molecular therapeutic strategy for NEDAMSS and IRF2BPL-related disorders.