In a school report card, each grade speaks for itself, but you can only tell how a student is doing overall by looking at the full report. For drugs that act on the brain, such a report card was missing for a long time. Every test on a miniature brain grown in a dish gave its own signal: some genes switched on, others switched off, electrical impulses sometimes sped up and sometimes went quiet. There was no way to pull these scattered data into a single score, and drug developers were stumbling in the dark.
To bring order, the researchers grew a special organoid that developed for 200 days and contained regions of the cortex, midbrain, brainstem, and even its own blood vessels. They exposed it to five drugs with different mechanisms, then collected data in four ways: they read gene activity in individual cells, measured proteins, and recorded electrical activity. Each method produced its own set of numbers, and comparing drugs with one another was impossible.
So the scientists created the Neural Impact Score, or NIS for short. The idea is simple: each gene, protein, and electrical parameter was pre-assigned a plus or minus sign depending on whether its change is favorable for the brain. These signs were then averaged within four categories: development, inflammation, degeneration, and cell resilience. A drug's final score is built from these four numbers, like a GPA on a school report card.
The results were surprising. Fingolimod earned the highest score, 1.06, landing in the green zone, while the popular antidepressant fluoxetine ended up only in the yellow zone with a score of 0.44. The comparison with rodent data was even more interesting: at the level of individual genes, the match was almost random, but at the level of the index categories, humans and mice agreed for some drugs. This means the index captures the big picture rather than the noise of individual measurements.
Pharmaceutical companies now have a common language for describing drug effects on neural tissue. This kind of report card can be applied to any organoid and even to other organs, such as the liver or heart. That would make screening drug candidates faster and cheaper, and reduce reliance on animal experiments.
The organoid grew for 200 days, roughly 6.5 months, which is comparable to the second trimester of a human pregnancy. In that time it formed 26 cell types, including cells of the vascular network.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.