PIM_CD
Research type
Research Study
Full title
Investigating PIM Kinase Inhibition as a Treatment for Coeliac Disease
IRAS ID
342986
Contact name
Hugo Penny
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS FT
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
The human gut contains a group of specialised cells, called intra-epithelial lymphocytes (IELs). These cells reside within the lining of the gut and play an important role in maintaining healthy gut function under normal conditions. In coeliac disease (CeD), IELs become inappropriately activated and damage the gut lining, which can cause symptoms associated with the disease and impair the body’s ability to properly absorb nutrients from food.
While the ability of IELs to cause gut damage reduces on a gluten-free diet (GFD), it persists in some individuals despite GFD adherence, such as those with refractory (R)CeD. Moreover, even in GFD patients, inadvertent gluten ingestion can rapidly activate IEL to damage the gut lining. Previous research has suggested that medications that block specific regulatory enzymes within IELs may reduce their ability to become activated and promote damage in the gut. However, little is known about this in the context of CeD and RCeD.
The aims of this project are to identify the mechanisms that allow IEL to become activated, and to investigate the potential of enzymes – such as PIM kinases – to drive IEL activation and their ability to cause tissue damage in CeD and RCeD. We aim to see what the effects are of blocking these enzymes in terms of IEL function in CeD and RCeD, and to identify the context within CeD guts that allows the activation of these enzymes.
Together, we believe that this project will help us to understand why gut damage occurs in CeD and shed light on possible treatments – such as PIM kinase inhibitors – that might be used to help treat patients with RCeD.
REC name
Wales REC 2
REC reference
24/WA/0271
Date of REC Opinion
20 Sep 2024
REC opinion
Favourable Opinion