OUR APPROACH
Start with evidence—not a predetermined treatment answer.
The collaborative will use a transparent readiness framework to evaluate disease mechanism, pathway direction, model systems, biomarkers, safety, and regulatory feasibility.
Mechanism review
Create a concise disease dossier covering gene function, pathway position, direction of dysregulation, affected cell types, developmental timing, and relevant literature.
Evidence grading
Separate direct evidence from inferred pathway relationships and identify the studies needed to close critical gaps.
Shared preclinical package
Use a reusable assay menu that may include RhoA-GTP, ROCK activity, LIMK/cofilin signaling, F-actin dynamics, neurite morphology, synaptic measures, and network function.
Safety and biomarker strategy
Define disease-specific risks, pediatric monitoring, pharmacology questions, and candidate measures of target engagement.
Regulatory pathway
Evaluate expanded access, early-phase clinical trials, basket-style approaches, master protocols, and disease-specific cohorts with appropriate expert guidance.
ROCK therapeutic relevance scorecard
| Question | What we look for |
|---|---|
| Pathway relationship | Direct regulation of RhoA/ROCK, or a strongly supported convergent mechanism |
| Direction | Evidence that signaling is increased, decreased, or context-dependent |
| Model evidence | Patient cells, iPSC-derived models, organoids, or animal models |
| Pharmacologic rescue | Normalization of relevant phenotypes with a ROCK inhibitor |
| Biomarkers | Feasible measures of safety, exposure, target engagement, and outcomes |
| Clinical readiness | Natural-history data, community engagement, and appropriate investigators |