Characterising and targeting the IL-17/IL-23 inflammatory axis in ankylosing spondylitis and inflammatory bowel disease (360G-Wellcome-102288_Z_13_Z)

£233,952

Compelling evidence implicates the IL-17/IL-23 inflammatory axis in ankylosing spondylitis (AS),rheumatoid arthritis (RA), as well as inflammatory bowel disease (IBD), with early clinical trials targeting this pathway in AS showing promising results. Central to this axis are innate and adaptive immune cells expressing the ROR-gammat transcription factor. Murine studies suggest that small molecules can directly inhibit ROR-gammat. However, It remains unclear which subset of patients or which diseases may be most responsive to blockade of this pathway, or which components of the axis are most critical. Firstly, I will characterize the IL-17/IL-23 axis in the blood and tissue of patients with AS and RA and compare these responses in collaboration with colleagues looking at IBD. Secondly I will compare the effects of ROR-gammat inhibitors with neutralizing antibodies on different classes of ROR- gammat-expressing cells including CD4+, CD8+, CD4-CD8-CD3+ and innate lymphoid cells. The key goals are to identify: 1) The cellular components of this inflammatory axis in the disease setting 2) The effects of inhibitors on the different cell types involved 3) Potential biomarkers for targeting therapy These studies would form the foundation for proof of concept clinical trials with therapeutic implications across the spectrum of inflammatory diseases.

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Grant Details

Amount Awarded 233952
Applicant Surname Al-Mossawi
Approval Committee PhD Studentships
Award Date 2013-06-24T00:00:00+00:00
Financial Year 2012/13
Grant Programme: Title PhD Training Fellowship for Clinicians
Internal ID 102288/Z/13/Z
Lead Applicant Dr Mohammad Al-Mossawi
Partnership Value 233952
Planned Dates: End Date 2016-07-31T00:00:00+00:00
Planned Dates: Start Date 2013-08-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East
Sponsor(s) Prof Rajesh Thakker