Why this pathway matters

Many rare genetic disorders affect proteins that sit upstream, downstream, or adjacent to RhoA–ROCK signaling. In some disorders, the pathway may be overactive; in others, underactive or context-dependent. The collaborative is therefore not based on the assumption that every actin-related disorder should receive a ROCK inhibitor.

Our goal is to determine which disorders have sufficiently strong, directional, and disease-relevant evidence to justify further testing.

Why fasudil is part of the discussion

Fasudil is a ROCK inhibitor with prior human use outside the United States and ongoing interest across several neurologic indications. That history may provide useful safety, pharmacology, manufacturing, and regulatory information. It does not establish that fasudil is safe or effective for any specific rare neurodevelopmental disorder.

The questions we need to answer

• Is RhoA–ROCK signaling altered in the disorder?
• Is the direction of dysregulation known?
• Is the mechanism demonstrated in patient cells or disease models?
• Does ROCK inhibition normalize relevant cellular or animal phenotypes?
• Are there measurable safety and target-engagement biomarkers?
• Is there a responsible regulatory and clinical path?