Karsten Carter suffers from XIAP deficiency, an exceptionally rare genetic condition that weakens the immune system. He is now 40, but since early childhood he has suffered from frequent infections, abscesses and severe gut inflammation needing multiple operations and long spells in hospital. XIAP deficiency occurs when mutations in the XIAP gene disrupt the body's ability to regulate immune responses. It is estimated to affect approximately 1 in 1,000,000 individuals in the UK - primarily males due to its link to the X chromosome. When it affects the bowel, it is usually mistaken for very severe Crohn’s disease, a form of inflammatory bowel disease (IBD).
Treatment of XIAP deficiency has focused on managing symptoms, controlling inflammation and treating complications. Long courses of steroids, as well as all the advanced therapies for Crohn’s disease have been tried, including stem cell (bone marrow) transplantation. Although two patients in Oxford have successfully been treated by a stem cell transplant, it carries a very high (25%) risk of mortality. So, Karsten is trying a new, experimental drug on a pioneering study at NDORMS, University of Oxford. The drug is called camoteskimab, a monoclonal antibody which targets a molecule called interleukin-18 (IL-18) that drives inflammation when the XIAP brakes controlling IL-18 come off. Camoteskimab is being developed by British company Apollo Therapeutics that is based in Oxford and Cambridge.
Under the care of Professor Simon Travis and Professor Holm Uhlig, the first dose of treatment was delivered at the Oxford Experimental Medicine Clinical Research Facility (EMCRF), part of the NIHR Oxford Clinical Research Facility (CRF). The EMCRF provides a resource for early phase, experimental research across the Medical Sciences Division at the University of Oxford and the OUH NHS Trust.
Professor Travis explained that they discovered Karsten's XIAP deficiency because they started testing the genetics of patients with severe Crohn's disease. While this testing is now routine for young children, it is not yet common for adults. ‘All of a sudden, we had a reason for Karsten’s exceptionally severe condition,’ said Simon.
‘Professor Uhlig identified very high levels of IL-18 in Karsten's blood. As there is no licensed treatment that targets IL-18 yet, we approached Apollo Therapeutics which is developing camoteskimab, an anti-IL-18 monoclonal antibody, to see if it could be used for Karsten.
‘The Apollo team was amazingly helpful and agreed to provide camoteskimab under an Expanded Access Program. After completing the necessary checks, we treated Karsten, who tolerated the infusion well and after just one week told me that he was already beginning to feel better.
‘This marks a significant step in precision medicine for inflammatory bowel disease, tailoring treatment to the specific cause of inflammation. The hope for the future is to identify precise causes of inflammation in people without a genetic reason for their IBD, enabling targeted treatments for all patients.’
Karsten said: ‘Let’s hope over time, I will notice a big improvement and be able to help the medical community to help other people to improve their lives.’
Dr Richard Mason, CEO of Apollo Therapeutics, said: ‘We are delighted to collaborate with the world-leading clinician scientists at the University of Oxford on their quest to develop precision medicines for patient’s inflammatory bowel disease.’