Development of new therapeutics for XIAP deficiency
Research type
Research Study
Full title
Development of new therapeutic strategies, including gene therapy and novel drugs, for X-Linked Inhibitor of Apoptosis (XIAP) deficiency
IRAS ID
260226
Contact name
Claire Booth
Contact email
Sponsor organisation
Great Ormond Street for Children NHS Foundation Trust
Duration of Study in the UK
2 years, 11 months, 31 days
Research summary
X-linked inhibitor of apoptosis (XIAP) is a ubiquitously expressed protein essential for a normal functioning immune system. XIAP deficiency is a devastating genetic condition where patients can develop various symptoms including life threatening, overactive immune responses to infection and inflammation of the gut leading to severe colitis. Haematopoietic stem cell transplantation (HSCT) is currently the only curative therapeutic option. However, transplant related mortality in these patients is high; survival for XIAP deficient patients is worse than we see in other conditions, with less than half surviving long term. We believe that gene therapy, where we insert a normal copy of the defective gene into the patients’ blood stem cells (HSCs), may offer patients with XIAP deficiency a safer and better treatment. We aim to demonstrate that targeted gene correction of the XIAP gene in patients’ blood stem cells, using the CRISPR/Cas9 system, is feasible, safe and results in restoration of protein expression and immune cell function. We will study this first in healthy donor and knock-out cell lines prior to testing in patient cells. Then we will investigate if transplantation of edited patient HSCs restores immune function in a mouse model. Additionally we will investigate mechanisms of immune dysregulation seen in XIAP patients, which may lead to repurposing of drugs used in other conditions.
REC name
London - Brighton & Sussex Research Ethics Committee
REC reference
22/LO/0860
Date of REC Opinion
15 Feb 2023
REC opinion
Further Information Favourable Opinion