Invention:
TMEM184B is a relatively uncharacterized 7-pass transmembrane protein that is a member of the Transporter-Opsin-GPCR (TOG) superfamily of proteins. It was discovered that over-expression of TMEM184B caused a reduction in scratching in response to interleukin-31 (Il-31) exposure. This was surprising given previous studies had shown that knock-out of TMEM184B resulted in a reduction in Il-31 induced scratching. Increasing the activity and/or abundance of TMEM184B in a patient may be used to treat itch.
Background:
Chronic itch affects up to 15% of the population. It may be caused by inflammation or more serious diseases of the kidneys, liver, nerves, and cancer. Chronic itch can impair quality of life, leading to disrupted sleep and anxiety / depression.
Somatosensory neurons transduce multiple types of stimuli, including temperature, chemical, and physical changes in the local environment of their nerve endings. Nerve endings receiving these cues can also directly sense inflammatory compounds, and this inflammation alters their response properties to cause hyperalgesia (heightened responses to noxious stimuli) and allodynia (painful responses to non-noxious stimuli). A common consequence of increased skin inflammation is the triggering of itch.
Acute and chronic itch are significant morbidities in humans. Itch-causing pathological conditions have a variety of causes, including skin disorders (atopic dermatitis), drug-induced reactions, systemic disorders such as liver disease, and other neurological disorders. The sensation of itch is distinct from pain and is carried by a subset of itch-specific somatosensory neurons called pruriceptive neurons with cell bodies in the dorsal root ganglia (DRG). Skin itch is triggered by release of pro-inflammatory compounds such as cytokines (IL-4, IL-13, and IL-31), thymic stromal lymphopoietin (TSLP), and histamine from mast cells and epithelial cells, which act upon membrane receptors and channels present in epidermal nerve endings. In addition to chemical itch, mechanical stimuli can evoke similar itch sensations but rely on a distinct spinal circuit.
Applications:
- Itch therapy, including chronic itch
Advantages:
- The therapy is specific for an itch sensation pathway that is different than a pain sensation pathway
