The Problem
Approximately 50 boys worldwide carry CASK gene variants. They have no disease-modifying treatment, no clinical trial, and no therapeutic pipeline. Each boy carries a different variant. The research infrastructure designed for large populations does not serve them.
Our son Anthony has a confirmed CASK splice-site variant with macrocephaly — an atypical presentation currently classified as a VUS. Not because there is evidence against pathogenicity, but because the classification system requires multiple unrelated cases that will never exist for a population this small. His medical team attributes his neurological findings to CASK. No one has performed the molecular work to determine what his variant does at the RNA level.
Without that data, no rational therapeutic approach can be designed. This study produces that data — and goes further.
What $50,000 Must Deliver
This study has four phases with defined deliverables. The Principal Investigator has full scientific authority over methods, experimental design, and interpretation. The deliverables are non-negotiable.
In Silico Characterization
Months 1–2
Computational splice prediction (SpliceAI, MaxEntScan, complementary tools) to identify predicted RNA consequences — exon skipping, cryptic splice activation, intron retention, NMD. Protein structural modeling of predicted aberrant products. Whole-genome and whole-exome sequencing data available immediately.
Deliverable: Computational variant report with predicted splice consequences and therapeutic amenability assessment.
RNA & Protein Confirmation
Months 2–6
Targeted wet-lab confirmation of in silico predictions. Minigene splicing assay or direct RT-PCR from patient-derived cells. Western blot to determine whether functional, truncated, or no CASK protein is produced. VUS resolved with direct experimental evidence.
Deliverable: Confirmed splice products, protein status, and therapeutic modality classification.
Preliminary Therapeutic Testing
Months 5–10
This is where $50K earns its keep. Once the splice defect is confirmed, test correction strategies in the same cell-based system: splice-switching ASO candidates, modified U1 snRNA, small molecule splice modulators, or pharmacological chaperones — determined by the Phase 2 data, selected by the PI.
Deliverable: 2–5 candidate therapeutic sequences or compounds with preliminary cell-based rescue data.
Pipeline Documentation
Months 10–12
Complete molecular classification report. All protocols, workflows, and decision frameworks documented for reuse. Manuscript preparation. Every tool built for this boy becomes reusable for the next.
Deliverable: Repeatable pipeline documented. Publication submitted. Next boy enters at reduced cost.
Who Should Apply
We are looking for a research partner — an academic lab, a contract research organization, or a collaborative team — with demonstrated capability in one or more of:
- RNA splicing biology and splice-site variant analysis
- Minigene assay systems and splice reporter design
- Antisense oligonucleotide design and testing
- Small molecule splice modulator screening
- Rare disease translational research
- CASK biology or synaptic scaffolding protein research
The PI will have full scientific authority over experimental methods, analytical approaches, and interpretation. CASK Warriors provides patient access, data, operational support, and funding. We do not direct scientific conclusions.
We do require that the work produces the defined deliverables on a 12-month timeline that advances toward therapeutic target identification. This is a partnership, not a grant with no strings attached.
