ALS – Amyotrophic Lateral Sclerosis

Functional motor neurons from patient iPSC lines to support ALS research and drug discovery

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease, characterized by the progressive loss of motor neurons and subsequent decline in muscle function. Despite advances in understanding disease biology, effective treatment options remain limited, highlighting the need for more predictive preclinical models. iPSC-derived motor neurons provide a human cell-based platform for studying ALS disease mechanisms and evaluating therapeutic candidates while preserving the genetic background of healthy and ALS patient donors.

Axol Bioscience offers extensively characterized iPSC-derived motor neurons from ALS donors carrying C9orf72 repeat expansion, TDP-43 A382T, and SOD1 D109Y mutations, alongside unaffected controls. Cells are available off-the-shelf and supported by optimized media, detailed protocols, and scientific support. Custom differentiation services are also available for isogenic cell types, including astrocytes and microglia.

Modeling ALS with iPSC-derived motor neurons, microglia and astrocytes

To support more complex ALS disease modeling, Axol Bioscience has developed human tri-culture systems incorporating iPSC-derived motor neurons, astrocytes, and microglia. Co-culture studies demonstrated that glial cells modulate motor neuron activity and network synchronization, highlighting the contribution of neuroimmune interactions to ALS-relevant phenotypes. These models enable investigation of cellular crosstalk and functional endpoints that are not observed in motor neuron monocultures.

Confocal images of control motor neurons cultured in monoculture (left) or in tri-culture with isogenic microglia and astrocytes (right). Images
were acquired at day 21 of motor neuron culture (microglia and astrocytes were introduced after cultures were established and were under co-culture
conditions for ~11 days). Green = CD44, Red = IBA1, Blue = Hoechst 33342, White = βIII-tubulin.

ALS iPSC lines

A  library of high-quality iPSC-derived lines from unaffected and patient donors, the portfolio is strengthened through strategic collaborations including the PRISM ALS consortia with LifeArc and ALS TDI to democratise access to diverse, patient-derived ALS models for researchers worldwide and other academic research institutes and patient advocacy groups.

PRISM lines

Through PRISM ALS, we are providing access to a diverse panel of motor neurons and other cell types from 14 sporadic ALS (sALS), patient lines. 3 familial ALS (fALS) and 3 control lines (gender diverse and age ranging 44-71), complemented by our in-house collection of familial, control, and asymptomatic donor-derived lines.

Product code	Product	Disease status	Age	Sex
ax0335	Motor neurons	sALS	51	F
ax0336	Motor neurons	sALS	58	F
ax0338	Motor neurons	sALS	71	M
ax0339	Motor neurons	sALS	50	M
ax0340	Motor neurons	sALS	58	M
ax0341	Motor neurons	sALS	61	F
ax0342	Motor neurons	sALS	44	M
ax0343	Motor neurons	fALS, SOD1 I114T	36	F
ax0344	Motor neurons	fALS, TARDBP N352S	59	M
ax0345	Motor neurons	sALS	61	F
ax0346	Motor neurons	sALS	69	F
ax0347	Motor neurons	sALS	66	M
ax0348	Motor neurons	sALS	68	M
ax0349	Motor neurons	fALS, C9orf72 affected	51	M
ax0350	Motor neurons	sALS	49	M
ax0351	Motor neurons	sALS	60	F
ax0352	Motor neurons	sALS	46	M
ax0353	Motor neurons	Unaffected	28	F
ax0354	Motor neurons	Unaffected	59	M
ax0337	Motor neurons	Unaffected	49	M

ALS familial mutation lines

Product code	Product	Disease status	Age	Sex
ax0074	Motor neurons	fALS, C9orf72 affected	64	F
ax0073	Motor neurons	fALS, C9orf72 – asymptomatic	62	M
ax0079	Motor neurons	fALS, TARDBP A382T	52	F
ax0735	Motor neurons	fALS, SOD1 D109Y	61	F
ax0076	Motor neurons	Unaffected	40-50	M

All cell lines can be custom differentiated into other cell types as requested.

Specialized services for ALS preclinical research and drug discovery

We apply our expertise in patient iPSC line generation and curation, along with our deep expertise in iPSC-derived in vitro models of neurodegeneration to support every stage of preclinical discovery from novel target validation to candidate selection. Our scientific and project management teams work collaboratively with clients to scope and deliver bespoke projects on a standalone or dedicated resource (FTE) basis.

Patient line derivation, banking and iPSC quality management

We work with patient advocacy groups and private and public research organisations to support line sourcing, ethics and consent review, primary material management, iPSC reprogramming, iPSC quality control, cell bank creation, expansion and custom differentiation. We currently maintain a library of >70 fully quality controlled iPSC lines and are actively building diversity and additional disease-relevance into the collection.

iPSC technical services

Services include large scale reprogramming projects, iPSC generation from primary material, iPSC quality control and gene-editing. Following generation of iPSC, or using client or commercially available lines, we provide manufacturing-scale differentiation to a range of cells including cortical excitatory neurons, interneurons, sensory neurons, striatal neurons, motor neurons, microglia, astrocytes, ventricular and atrial cardiomyocytes, cryopreservation where appropriate and functional quality control.

In vitro model and assay development and validation

Services include complex model development in monoculture and co-culture, custom protocol design and optimization, model characterization, phenotypic analysis, treatment titration and endpoint assays, integration with MPS and other platforms and collaborative scale-up for transfer to higher throughput platforms and CRO, or in-house workflows.

Candidate drug testing in iPSC models

Services include compound, viral delivery vectors or novel mechanism drug toxicity and effect screening using optimised in-house assays including multi-electrode array (MEA), flow cytometry, cellular imaging, real-time imaging, plate-based assays and ‘omics.

Assays commonly utilized in ALS-related projects

We are actively collaborating with multiple large organisations pursuing new therapeutic avenues for ALS/MND and provide reprogramming, custom banking and distribution or licensing.Service project provision is available for the evaluation of new compounds, viral vectors or combinations and these frequently include assessing functionality of neurons by MEA or IncuCyte based spontaneous neuronal activity measurements. In addition, effects on cell toxicity and morphology are assessed by tracking neurite outgrowth and utilising ATP/LDH based cell health assays on both motor neurons and microglia derived from ALS patients. To support new developments in the field, we are developing further reproducible assays, including Neurofilament light (NFL) quantification, TDP-43 aggregation (imaging and HTRF based), cryptic exons and developing functional tri-culture models with motor neurons, astrocytes and microglia to evaluate neuroinflammatory aspects.
We are always happy to discuss and help scope your project requirements. Please email operations@axolbio.com to arrange a technical call with our scientific leads.