Science
ONL Therapeutics’ primary scientific focus is Fas-mediated signaling, initiated by the activation of the Fas receptor at the cell surface and implicated in a variety of diseases
How the Fas-Blocking Mechanism of Action Works
Targeting Fas prevents activation of downstream death pathways and the inflammatory cascade that accelerates cell death and tissue damage. ONL’s lead therapeutic candidate, ONL1204, is a small peptide Fas inhibitor designed to protect retinal cells and preserve vision in a range of blinding diseases.
Disease Stress Leads to Fas Activation in Retinal Cells and Induces Fas Signaling, Which Triggers:
Cell death signaling cascades
Initiation of the production of chemokines and cytokines
Chemokines and cytokines contribute to the inflammatory microenvironment and recruit additional immune cells that bring more Fas ligands to the retina
Fas-mediated signaling is considered one of the body’s cornerstone mechanisms for activating cell death. Death of vital cells is a root cause of a host of diseases and conditions and has been specifically associated with many ophthalmic diseases.
In addition to its close association with cell death, Fas also plays a role in regulating immune signaling and associated inflammation. This distinct function of Fas is becoming more widely understood and appreciated. Fas-mediated immune signaling can induce additional cell death, increase damage to the surrounding tissues, and worsen the initial injury from the disease.
Fas-mediated cell death and immune signaling have been implicated in the development and progression of many diseases and conditions. ONL and others have demonstrated vital roles for Fas in a wide range of retinal disease, including retinal detachment, dry and wet age-related macular degeneration, uveitis, diabetic retinopathy, glaucoma, and optic neuropathies.
Inhibition of Fas signaling at the receptor represents the most direct and upstream approach to preventing its negative impact. ONL believes that the therapeutic benefits of blocking Fas activation and its subsequent signaling may have wide-ranging clinical value for patients suffering from retinal diseases.