28bio | Safety

Improve patient safety by predicting CNS neurotoxicity with greater accuracy

A study published in ALTEX found that CNS-3D Organoids were 7.41 times more accurate than traditional animal models at predicting clinical neurotoxicity because they contain multiple iPSC-derived neural cell types that capture the complexity of human brain tissue. Unlike basic cell cultures, CNS-3D Organoids measure functional electrical activity, enabling detection of early changes in neural network behavior that may indicate toxicity before structural damage occurs.

Dose response data of 8 representative compounds with various degrees of toxicity as assessed by potency of neuromodulation (peak count) relative to clinically relevant concentrations (Cmax).

Key Benefits

COMPREHENSIVE
ANALYSIS

Leverage multiple functional metrics into an integrated neurotoxicity scoring system for clear compound evaluation.

QUALIFIED
PERFORMANCE

Independently verified across 84 compounds with known clinical outcomes, demonstrating reliable translation.

MECHANISTIC
INSIGHTS

Heat map analysis reveals functional signatures that cluster by mechanism of action, providing deeper understanding of how compounds affect neural function.

Improve patient safety by predicting peripheral neuropathy before the clinic

PNS-3D technology uses human-derived sensory neurons and Schwann cells in a 3D microenvironment — capturing the complex biology of the peripheral nervous system. Custom embedded electrode arrays record both structural and functional changes in nerve conduction for a comprehensive and mechanistic assessment.

Stacked nerve-conduction traces captured pre-dose (top) and post-dose (bottom) track the same axons over time; blue-highlighted baseline signals recorded at increasing electrode distances visualize the propagating compound action potentials that define nerve-conduction velocity. After chemotherapeutic dosing these distance-dependent responses vanish, revealing a marked loss in signal amplitude and conduction speed.

Key Benefits

FUNCTIONAL
ANALYSIS

Measure actual nerve conduction changes, providing insights beyond simple cell viability assessments.

CLINICALLY RELEVANT
METRICS

Capture electrophysiological markers used in clinical neuropathy diagnosis, enhancing translation to human outcomes.

DOSE-RESPONSE
CHARACTERIZATION

Establishes clear safety margins for peripheral nerve effects across multiple concentration ranges.

LONGITUDINAL
ASSESSMENT

Track the development of neuropathy over extended exposure periods, revealing cumulative effects that acute studies might miss.

INTEGRATED
EVALUATION

Five distinct functional metrics combine into a Velocity Density Index (VDI), enabling straightforward compound ranking and comparison.

Improve patient safety by predicting peripheral neuropathy in ADCs and chemotherapeutics

Identify safer therapeutic candidates by evaluating off-target peripheral neuropathy risks from Antibody-Drug Conjugates (ADCs) and chemotherapeutics with iPSC-derived sensory neurons and primary Schwann cells. By measuring neurite outgrowth and Schwann cell morphology after exposure to known peripheral neuropathy-inducing agents, compound-specific toxicity profiles can be identified.

IC50 dose–response profiles for four chemotherapeutics overlay functional electrophysiology (black) with nerve morphology (blue), exposing compound-specific separations between early activity loss and later structural damage that inform mechanism of action.

Key Benefits

ADC & SMALL MOLECULE
SCREENING

Rank-order chemotherapeutic candidates by peripheral neuropathy risk.

ADC OPTIMIZATION

Compare the neurotoxic potential of different linker-payload combinations.

NEUROPROTECTION
EVALUATION

Test potential protective therapies alongside cancer treatments

Identify Toxicity with Human CNS and PNS Organoids

Safety Applications

Preclinical Safety Resources