Neuronal S1PR3: A Biomarker And Therapeutic Target For Acute And Chronic Itch

Tech ID: 27082 / UC Case 2017-029-0

Patent Status

Country Type Number Dated Case
United States Of America Published Application 20180110757 04/26/2018 2017-029
 

Brief Description

S1PR3 activation via its endogenous ligand (S1P) or a specific agonist evokes dose-dependent acute itch. 
S1PR3 activation via S1P at high doses evokes thermal but not mechanical pain. 
S1PR3 is expressed by a subset of nociceptors and pruriceptors which express the TRPA1 and TRPV1 ion channels, known to transduce itch and pain. 
S1PR3 activation evokes neuronal excitability via its stimulating actions on TRPA1 and TRPV1. 
S1PR3 activation evokes itch via TRPA1 and pain via TRPV1. 
S1PR3 gene expression is elevated in skin and sensory neurons in a mouse model of atopic dermatitis (eczema).  

Suggested uses

Diagnostic applications for chronic itch and chronic pain, treatment for eczema, treatment for allergic itch, treatment for acute and chronic pain, treatment for neuropathic pain

Advantages

Possible advantages include specificity for all itch-sensing neurons and applicability to multiple chronic itch diseases, as S1PR3 is expressed not only in the population of neurons that sense allergic itch, but also in neurons that sense other forms of itch. Additionally, new antagonists to S1PR3 are currently being designed and tested by others; so many possible therapeutic options will exist in the near future. Furthermore, S1PR3 is relatively specific to sensory neurons compared to the other four S1P receptors, so blocking S1PR3 will specifically target sensory neurons without unwanted side effects on the immune system or central nervous system, where it is not highly expressed2,3. Finally, while TRPA1 blockers exist, these have not yet proven to work effectively in humans for chronic itch. Therefore, it is important to examine multiple itch pathways, such as S1PR3. Possible disadvantages include: poor solubility or permeability into the skin of current S1PR3 antagonists and low levels of effectiveness if multiple itch pathways are involved in a particular condition.

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Inventors

  • Bautista, Diana M.

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