NAMs in Neuroscience
Brain organoids, blood-brain barrier models, and human-relevant approaches to understanding neurological diseases—because the human brain is unlike any other species
The Neuroscience Translation Problem
The human brain is the most complex organ, with unique cell types, connectivity patterns, and disease mechanisms not found in other species. Mouse models have consistently failed to predict human responses in neurological diseases—particularly Alzheimer's, where over 200 drugs that worked in mice have failed in human trials. Human brain models are essential.
Blood Side
Drugs circulate in the bloodstream but cannot freely enter the brain
Brain Side
Protected environment where neurons require precise drug concentrations
Human BBB models are critical because mouse BBB has different transporter expression and permeability
Human Brain Models
NAMs that capture human-specific neurobiology
Brain Organoids (Cerebral Organoids)
3D structures grown from human iPSCs that self-organize into brain-like tissue with distinct regions and cell types.
- ✓ Multiple brain cell types
- ✓ Spontaneous electrical activity
- ✓ Models neurodevelopment
- ✓ Patient-derived disease models
BBB-on-Chip
Microfluidic devices that recreate the blood-brain barrier with human endothelial cells, pericytes, and astrocytes.
- ✓ Tests drug BBB penetration
- ✓ Flow conditions like blood vessels
- ✓ Human transporter proteins
- ✓ Disease-state modeling
Neural Spheroids
Smaller, simpler 3D neural cultures for high-throughput screening of neurotoxicity and drug effects.
- ✓ Rapid, scalable production
- ✓ Neurotoxicity screening
- ✓ Synapse formation
- ✓ Cost-effective
Multi-Electrode Arrays (MEAs)
Platforms that record electrical activity from human neurons to study neural network function and drug effects.
- ✓ Real-time activity monitoring
- ✓ Seizure liability detection
- ✓ Network connectivity analysis
- ✓ Functional readouts
Neurological Disease Modeling
Using human cells to understand brain diseases
Alzheimer's Disease
Model amyloid plaques and tau tangles in human neurons that carry patient mutations (APP, PSEN1).
Parkinson's Disease
Study dopaminergic neuron degeneration using iPSC-derived midbrain organoids from PD patients.
ALS (Lou Gehrig's Disease)
Investigate motor neuron death using human motor neurons derived from ALS patient cells.
Epilepsy
Study seizure activity using human neural networks on MEAs and brain organoids.
Brain Tumors (Glioblastoma)
Test drugs on patient-derived glioblastoma organoids that retain tumor heterogeneity.
Multiple Sclerosis
Model demyelination and immune attack on oligodendrocytes using human cell systems.
Human vs. Mouse Brain
Critical differences that affect drug development