ideasIdea
Build a human model of the barrier that guards the brain fluid
Drugs that reach brain tissue may still fail to reach the fluid where cancer spreads along the linings. A lab model of that second barrier would let us screen for drugs that cross it.
Leptomeningeal disease is governed by the blood-cerebrospinal fluid barrier at the choroid plexus, which differs from the blood-brain barrier in transporters and tight junction composition. Stem-cell-derived choroid plexus organoids that produce cerebrospinal fluid-like secretion have been reported, giving a human in vitro system for screening cerebrospinal fluid penetration and for studying how tumour cells survive in that nutrient-poor compartment.
Hypothesis
Choroid plexus organoid permeability ranks drugs concordantly with measured human cerebrospinal fluid-to-plasma ratios, making it a usable screening assay for leptomeningeal indications.
Rationale
Leptomeningeal metastasis is uniformly lethal and increasingly common as systemic control improves, yet drug selection for it is guesswork. A quantitative human assay for the correct barrier is a prerequisite for rational selection.
What would test it
Benchmark organoid permeability against 20 drugs with published human cerebrospinal fluid-to-plasma ratios; report rank correlation and cost per compound.
Maturity
preclinical evidence
Who has to act
engineering
Cost to try
Medium ($1M to $50M)
Years to first evidence
6
Bottlenecks it attacks
- The brain: barrier and sanctuary · Most drugs cannot cross into the brain, so brain tumours and brain metastases lag every other site.
- Preclinical models that do not predict people · Nine in ten cancer drugs that work in mice fail in humans. Our models are the reason.