ALS-00T2

ALS-00T2 is an orally bioavailable, peripherally and centrally active small molecule antagonist of the P2X7 receptor, currently being developed by Alsonex for the treatment of Amyotrophic Lateral Sclerosis (ALS). The P2X7 receptor is a trimeric, ligand-gated ion channel that is activated by high concentrations of extracellular ATP, typically released during cellular stress or injury. In the central nervous system, P2X7 is predominantly expressed on microglia, where its activation serves as a key "second signal" for the assembly of the NLRP3 inflammasome. This process leads to the maturation and secretion of potent pro-inflammatory cytokines, including interleukin-1β (IL-1β) and interleukin-18 (IL-18), which contribute to chronic neuroinflammation and neuronal death. By selectively inhibiting P2X7, ALS-00T2 aims to dampen this neuroinflammatory response and preserve motor neuron function. The compound has undergone Phase 1 clinical evaluation to assess its safety, tolerability, and pharmacokinetics in healthy volunteers and patients.