Next steps and collaboration
Immediate validation priorities (weeks to months)
The single highest-value step is a retrospective cohort comparison at specialized PACS1 clinics — see page 10. We are actively reaching out to clinicians at CHU Montpellier (Pr Geneviève) and welcome contacts elsewhere.
Next steps in increasing complexity:
Step | Time | Estimated cost | Lab type |
Retrospective cohort analysis | 4–12 wk | ~0 € | clinical (PACS1 specialist) |
Thermal shift / SPR binding assay | 4–8 wk | ~5–15 k€ | biochemistry |
Cellular rescue assay (TGN46, COL8A1) | 12–24 wk | ~30–50 k€ | cell biology |
Molecular dynamics 100 ns × 3 (GPU) | 1–2 wk | ~0–500 € | computational |
Pocket #1 stability MD + ligand docking | 2–4 wk | ~0–1 k€ | computational |
Cryo-EM or X-ray of bound complex | 6–18 mo | ~50–150 k€ | structural biology |
Prospective stratified clinical trial | years | ≥ 500 k€ | clinical trial |
Collaboration calls
We invite contact from researchers and clinicians with:
- PACS1 patient cohorts with documented mutation status and outcome data
- Recombinant protein expertise — would your group purify PACS1-FBR (residues 100–280) for SPR/ITC binding studies?
- Cell biology / iPSC-neurons — patient-derived lines for rescue assays
- GPU resources for MD simulation
- Medicinal chemistry interest in next-generation R203W-selective binders (the pharmacophore framework is on page 7)
Contact: [email protected] or via OSF project ed7sp.
What we will not do
For transparency:
- We will not treat any individual patient based on this work. Recommendations belong with treating clinicians.
- We will not issue press releases prematurely. The next milestone is the retrospective cohort result.
- We will not make commercial claims. The drugs cited are FDA-approved with widely available generic versions.
Documents prepared for clinicians
A scientific note for Pr Geneviève (CHU Montpellier) summarizing the phenytoin hypothesis and proposing the retrospective analysis is available on OSF (Note_PACS1_Pr_Genevieve_v2.pdf). A 2-page family letter (Lettre_a_Julien_PACS1.docx) is also available for patients/families who wish to understand the work.