Functional motor neurons from patient iPSC lines to support ALS research and drug discovery
In vitro models for ALS/MND drug discovery
ALS (amyotrophic lateral sclerosis) is the most common form of motor neuron disease, where the progressive destruction of motor neurons leads to loss of muscular function. With limited treatment options and a predicted 69% increase in cases by 20402, attention has turned to implementing in vitro ALS models that use human-induced pluripotent stem cell (iPSC)-derived cells from healthy or patient donors to accelerate preclinical drug discovery.
The cells retain the disease characteristics and genetic background of the donor, enabling researchers to generate more predictive in vitro ALS models for basic research and drug discovery.
Major cell types involved in ALS
Motor neurons
Central to ALS pathophysiology is the progressive destruction of motor neurons, preventing effective communication between the brain/spinal cord and muscles.
axoCells motor neurons are functionally active in 10 days and demonstrate key marker expression (including HB9 and ChAT) and functional relevance in assays including electrophysiology and calcium imaging. ALS patient donor-derived motor neurons that carry known mutations, such as in C9orf72 (ax0074), demonstrate phenotypic and functional differences compared to healthy donor -derived motor neurons, including more fibrous neurites and higher firing frequency.
Microglia
An overlap has been observed between neurodegenerative disorders, ALS and frontotemporal dementia (FTD) with several genes implicated in both diseases, including C9orf72, the most common cause of familial ALS. Neuroinflammation is thought to be an important contributor to the pathology of both of these diseases.
axoCells microglia are assay-ready in 7days and express key markers (includingIba1, TMEM119, CX3CR1 and P2RY12), with functional relevance in assays including phagocytosis, chemotaxis and cytokine release. ALS-derived microglia (C9orf72) exhibit reduced phagocytosis of myelin basic protein compared to healthy control.