ALS – Amyotrophic Lateral Sclerosis

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 functions including walking, talking, swallowing and breathing. There is currently no cure. With treatment aimed at symptomatic relief and prolonging survival, most patients live only 3-5 years from the onset of symptoms.

With limited treatment options and a predicted 69% increase in cases by 2040, attention has turned to in vitro ALS models that use human iPSCs from healthy or ALS patient donors.

The cells generated from these iPSCs retain the characteristics of their donors, enabling researchers to generate in vitro ALS models to improve knowledge of the disease or to screen potential therapies on a more human-relevant platform.

Axol offers:

• Functional Motor neurons generated from ALS donors
• Custom made-to-order differentiated human iPSC-derived motor neurons and microglia
• ALS model building, relevant assays and model characterization
• ALS compound testing on iPSC models

Motor neurons: Central to ALS pathophysiology is the progressive destruction of motor neurons, preventing communication between the brain/spinal cord and muscles.

axoCells Motor Neurons arefunctionally active in 10 days and demonstrate key marker expression (including HB9 and ChAT) and functional relevance in assays including electrophysiology and calcium imaging. Our ALS-derived motor neurons (ax0074, C9orf72 mutation) demonstrate phenotypic and functionaldifferences compared to healthy control-derived motor neurons, includingmore fibrous neurites and higher firing frequency.

Microglia: There is an overlap between ALS and frontotemporal dementia (FTD) with several genes implicated including C9orf72, the most common cause of familial ALS. As the main neuroinflammatory cell of the brain, microglia can be used to model the ALS-FTD overlap

Our 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.

Introducing the axoCells ALS Toolbox 

Axol Bioscience, leader in iPSC technology had launched the axoCells ALS Toolbox to support drug discovery and research into amyotrophic lateral sclerosis (ALS).  

The toolbox includes motor neurons from six different donor lines including two unaffected donors, one C9orf72 carrying donor (a sibling to one of the ALS donors), and three donors each carrying significant genotypes associated with ALS, SOD1, C9orf72 and TDP43.