Therapeutics: Interleukin-1 (IL-1) β; IL-1 receptor; purinergic receptor P2X ligand-gated ion channel 7 (P2RX7; P2X7)

In vitro and mouse studies suggest inhibiting P2RX7 or IL-1β/IL-1 receptor signaling could help treat AMD. Subretinal accumulation of chemokine CX3C motif receptor 1 (CX3CR1)-deficient mononuclear cells causes photoreceptor degeneration in AMD. In mouse retinas, CX3CR1 deficiency increased levels of P2RX7 on monocytes and, in turn, increased P2RX7-induced secretion of IL-1β by monocytes, compared with normal CX3CR1 expression. In a CX3CR1-deficient mouse model of AMD, intravitreal injection of a P2XR7 antagonist or an IL-1 receptor antagonist decreased subretinal photoreceptor degradation compared with vehicle. Next steps could include testing inhibitors of P2RX7 and IL-1β/IL-1 receptor signaling in additional models of AMD.

Evotec AG and Zhejiang Conba Pharmaceutical Co. Ltd. have the P2RX7 antagonist EVT401 in Phase II testing to treat inflammation...