Reviewed by Sarah Alter, Ph.D. — Scientific Affairs, OrganaBio. 15 years of immunology research spanning autoimmunity, cancer, and infectious disease. University of Miami Miller School of Medicine. Registered Patent Agent.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss, and it has a neuroinflammatory component that has become an increasingly active therapeutic target. Peripheral blood monocytes, T cells, and NK cells from ALS patients show distinct activation patterns that reflect CNS-directed neuroinflammation, microglial priming signals, and TDP-43/SOD1/C9orf72 mutation-associated immune dysregulation. PBMCs from ALS donors are used in monocyte activation assays, T cell phenotyping for neuroprotective vs. neurotoxic subsets, and pharmacodynamic studies for emerging ALS immunomodulatory candidates.
Neuroinflammation in ALS and Its Peripheral Immune Signature
ALS neuroinflammation is driven by both resident CNS cells (microglia, astrocytes) and peripheral immune infiltrates. Circulating monocytes are recruited to the CNS and differentiate into CNS macrophages that amplify motor neuron death through reactive oxygen species and inflammatory cytokines. CD4+ T cells in ALS shift from neuroprotective regulatory phenotypes (Tregs, Th2) toward neurotoxic Th1 and Th17 profiles as disease progresses. This T cell phenotype shift correlates with disease progression rate and is a pharmacodynamic endpoint for immunomodulatory candidates. NK cell cytotoxicity is elevated in some ALS patients and may contribute to CNS damage, though the NK cell role remains less defined than monocyte and T cell contributions.
OrganaBio ALS Donor Catalog
| Attribute | Available |
|---|---|
| ALS subtype | Sporadic (sALS) and familial (fALS) documented; SOD1, C9orf72, TDP-43 mutation status where available |
| Disease duration / ALSFRS-R | Available on select lots; rate of progression documented where known |
| Onset type | Limb-onset and bulbar-onset documented |
| Ventilatory status | Documented; early vs. late disease |
| PBMC format | Cryopreserved; fresh on scheduled collection |
| Lot documentation | CoA, ALS subtype, mutation status, ALSFRS-R, onset type, flow cytometry |
Key Cell Populations for ALS Research
- Classical monocytes (CD14++/CD16–): Elevated activation markers and IL-6, TNF-α production in ALS; CNS recruitment amplifies neuroinflammation; primary target of monocyte-directed ALS immunotherapy candidates
- CD4+ T cells (Th1/Th17 vs. Treg): Th1/Th17 expansion correlates with faster ALS progression; Treg:Teff ratio is an immunological disease progression marker; neuroprotective role of Tregs is supported by ALS mouse model data and pilot human studies
- CD8+ T cells: Activated and CNS-infiltrating in late ALS; cytotoxic T cell markers elevated in faster progressors
- Regulatory T cells (FoxP3+): Reduced in ALS and inversely correlated with disease progression rate; pharmacodynamic target for IL-2 low-dose therapy and Treg expansion approaches
- NK cells: Altered cytotoxicity in some ALS patients; potential contributor to motor neuron damage; less studied than T cell and monocyte compartments
Research Applications
- Monocyte activation characterization: LPS-stimulated cytokine profiles (IL-6, TNF-α, IL-1β) in ALS vs. healthy PBMCs as neuroinflammation readout
- T cell phenotype progression correlation: Treg:Teff ratio and Th1/Th17 balance as pharmacodynamic biomarkers for ALS immunomodulatory candidates
- Low-dose IL-2 therapy pharmacodynamics: Treg expansion monitoring in ALS PBMCs from IL-2-treated donors
- SOD1/C9orf72 mutation-stratified immune phenotyping: familial vs. sporadic ALS immune differences
- Biomarker discovery: neurofilament light chain (NfL) and immune activation marker correlations in peripheral blood
- iPSC-derived motor neuron co-culture: PBMC-derived monocyte and T cell populations in ALS-relevant neurotoxicity models
