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Chemotherapy-induced Peripheral Neuropathy (CiPN)Case studies demonstrating iCell Neuron use

Chemotherapy-induced peripheral neuropathy (CIPN)

• Most common non-hematological side-effect

• Estimated 12 million cancer survivors in 2012

• CIPN can affect 20-40% of patients

• Limits therapeutic options

This slide deck summarizes published literature validating

iCell Neurons as a model for CiPN and the underlying genetics

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Case Study #1: iPSC Neurons and Chemotherapy induced Peripheral Neuropathy (CIPN)

Chemotherapeutics affect neurite outgrowth of iPSC neurons

Can this be used as an endpoint to understand the genetics of CIPN?

PLOS ONE, 2015

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Chemotherapeutic-induced Neuropathies Layering in Diversity: Associating population genetics with function

Mean most sensitive: NA12892 and NA12814

Mean most resistant: NA07022 and NA12752

Observed reproducible

differences in morphological

characteristics among different

drugs and genetically diverse

neurons for each drug

Establishes a framework for

functional studies of genes

contributing to CIPN and

identifying drugs to treat or

prevent CIPN

iPSC-Neurons from 4 different unrelated LCLs

with varying degrees of chemotherapeutic toxicity

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Case Study #2:

Proof of concept for iPSC neurons and CiPN

• Inherited polymorphism in CEP72 is associated with risk and severity of

vincristine-induced neuropathy in children with ALL.

• Polymorphism reduces CEP72 expression

• Knock-down of CEP72 expression in iCell Neurons results in increased

sensitivity to vincristine compared to control iCell Neurons.

POC #2 passed

Can this be extended to

the clinical population?

JAMA, 2015

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Case Study #3:

Functional Validation of Genetic Variants Associated with Paclitaxel-induced Cytotoxicity

Decreased AIPL1 expression reduces sensitivity

of human iPSC-derived neurons to paclitaxel

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Case Study #4: Consistent Material Enables Robust Phenotypic Assays

Stem Cell Res, 2016

Different batches of iPSC-Neurons derived from a single iPSC clone showed:

• No significant differences in transcriptomic profiling

• Consistency in gene expression, cytosine modifications, neurite growth

• No significant differences in sensitivities to paclitaxel, vincristine, and cisplatin

Effect of chemotherapeutic agents on neuronal

outgrowth compared between neuron batches

Profiling of iPSC

differentiated neurons

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Case Study #5:Evaluate effects of chemotherapeutic agents on iPSC neurons structure and function

iCell Neurons are able to identify

compounds that are protective for

CiPN

CiPN compounds have an effect on

Neuronal electrical activity

iCell Neurons are able to detect CiPN

by different mechanisms