Background:
Severe itch (or pruritus) is associated with multiple diseases such as liver disease, non-Hodgkin’s lymphoma, psoriasis, and common eczema and is also a side effect of many treatments including analgesics (like morphine) and renal dialysis. Chronic pruritus is a top reason for dermatologist visits, yet there is no effective treatment for patients suffering from histamine-independent chronic pruritus. One major obstacle to effective treatment of itch is that no itch-specific genes suitable as drug targets have been identified. In addition, itching has been regarded as a less intense version of the body’s response to pain, thereby making itch-specific therapy difficult to achieve without affecting pain responsiveness.

Technology Description:
The described invention encompasses novel methods for treating pruritus in humans and animals based on a newly defined itch mechanism. Dr. Zhou-Feng Chen has identified the first itch-specific receptors, including gastrin-releasing peptide receptor (GRPR) and neuromedin B receptor (NMBR), as central mediators for the itch signal. Furthermore, Dr. Chen has demonstrated that responses to pain and itch represent independent signaling pathways and inhibiting the itch pathway can be used for treatment of patients afflicted with pruritus.

Dr. Chen has shown that itch can be relieved by delivery of antagonists directed to the receptors using a multi-pronged genetic and pharmacologic approach. GRPR or GRPR/NMBR-double null mice treated with pruritic-inducing agents exhibited significantly reduced scratching relative to wild-type mice. Similarly, when wild-type mice were treated with an intrathecal administration of GRPR, NMBR or GRPR and NMBR antagonists, the mice exhibited virtually no scratching behavior in response to itch-inducing analgesics like morphine or other itch-inducing compounds. Comparable results were seen when these antagonists were used to relieve itch in mice with atopic dermatitis, suggesting that GRPR and/or NMBR antagonists can be used to treat both acute and chronic itch problems.

A distinct therapeutic approach also encompassed by the invention involves selective and targeted ablation of spinal cord neurons expressing GRPR. Wild-type mice that were injected with a bombesin-saporin (GRPR ligand conjugated to a neurotoxin) exhibited complete itch relief but importantly still maintained normal pain responses and normal motor neuron function. Mice with chronic itch (atopic dermatitis) that were treated with bombesin-saporin also exhibited complete itch relief through GRPR neuron ablation in the spinal cord.

File Number: 6757 

Other Information:

Publication: Nature 2007; 448: 700-3.