A researcher from the University of Pittsburgh has identified a glutamate receptor antagonist to suppress mast cell function.
Description
Cutaneous mast cells underly many of the processes involved in skin inflammation. They also have anatomical and functional associations with sensory afferent neurons. Studies have shown ablation of a subset of sensory nonpeptidergic neurons expressing MrgprD increased mast cell degranulation leading to cutaneous inflammation. MrgprD-expressing neurons are known to release glutamate to suppress mast cell reactivity. This approach utilizes glutamate receptor agonists to mimic this response to suppress the activation of cutaneous mast cells. Suppression of activation of cutaneous mast cells could provide treatment options for a wide range of skin conditions.
Applications
• Dermatitis
• Rosacea
• Contact hypersensitivity
Advantages
Current approaches to suppressing cutaneous mast cell activity are not highly effective. This approach is designed to target glutamate receptors on cutaneous mast cells, reprogramming these cells to a state of low responsiveness.
Targeting glutamate receptor agonists has previously shown promise in treating central nervous system conditions including Parkinson’s disease, and this novel approach will use glutamate receptor agonists to target immune cells in the periphery.
Invention Readiness
In vivo data has shown SYM2081 can suppress mast cell activation. Research has identified the kainate receptor GluR6/KA2 as the glutamate receptor subtype expressed on dermal mast cells. A highly selective GluR6 agonist SYM2081 was identified and shown to suppress degranulation of PCMC in response to MrgprB2 in vitro. In vivo studies showed SYM2081 delivered intradermally or interperitoneally can suppress induced-dermal mast cell activation and induced dermatitis.
IP Status
https://patents.google.com/patent/US20240342136A1