Hyperactivated effector T cells and pro-inflammatory myeloid cells

Hyperactivated effector T cells (Teffs) and pro-inflammatory myeloid cells, including activated microglia and macrophages, are central drivers of the neuroinflammatory cascade in Amyotrophic Lateral Sclerosis (ALS) (Appel et al., 2021, JCI Insight). In ALS patients, the homeostatic balance between neuroprotective regulatory T cells (Tregs) and neurotoxic Teffs is typically disrupted, creating a pro-inflammatory environment that accelerates motor neuron degeneration (Beers & Appel, 2019, Nature Reviews Neurology). These hyperactivated cells release high levels of neurotoxic cytokines and reactive oxygen species that directly contribute to neuronal death. Therapeutic strategies, most notably the combination therapy COYA 302, target this cellular axis by suppressing the activity of Teffs and myeloid cells while simultaneously boosting the number and suppressive function of Tregs (Coya Therapeutics, 2023). By shifting the immune system from a pro-inflammatory to an anti-inflammatory state, these interventions aim to slow disease progression and preserve motor function in ALS patients.

Other names

TeffsPro-inflammatory macrophagesM1-like microgliaNeurotoxic immune cell populationActivated T-effector/Myeloid axis

Simultaneous suppression of pro-inflammatory effector T cell (Teff) activity and myeloid cell signaling (e.g., via CTLA4-Ig) while enhancing the suppressive function of regulatory T cells (Tregs) to restore immune homeostasis.