Investigating small molecules to treat XLP
Research type
Research Study
Full title
Investigating small molecules to treat X-linked lymphoproliferative disease (XLP)
IRAS ID
263982
Contact name
Claire Booth
Contact email
Sponsor organisation
Great Ormond Street Hospital
Duration of Study in the UK
4 years, 11 months, 27 days
Research summary
X-linked lymphoproliferative disease (XLP) is a rare genetic immune disorder affecting boys. Symptoms vary but most patients have abnormal immune responses to some viral infections and about a third develop lymphoma. Affected boys become sick in childhood or early adolescence and the disease can be rapidly fatal. We can offer bone marrow transplant as a curative treatment but results depend on having a well matched donor and preferably transplant before any symptoms develop. Our group is also developing gene therapy approaches to treat XLP patients lacking a suitable donor for transplant. Still, the need for
alternative treatment options in patients with this condition is profound. The dysfunctional protein in XLP, called SAP, acts as a key player in immune cell signalling. It is critical for immune cells to work properly but its role is not entirely clear. Recently a drug has been developed for use in cancer therapy which acts along the same pathways that are defective in XLP and early data suggests that this drug could improve the immune dysfunction in XLP patients. Potentially this could be used to keep patients as well as possible whilst awaiting a bone marrow transplant. We will test the compound on patients’ cells in the laboratory to determine if it can effectively correct the immune abnormalities and we will further investigate how cell signalling pathways in XLP are disrupted and why this leads to clinical symptoms. If we can show this drug may be of clinical benefit to patients we will seek further funding to undertake the required studies to progress to clinical trial. Given that similar drugs are already being used in clinical trials for certain forms of cancer and that XLP is a rare disease, the pathway to clinical use could be accelerated with trials commencing within the next two years.REC name
London - Surrey Research Ethics Committee
REC reference
19/LO/0720
Date of REC Opinion
24 Apr 2019
REC opinion
Favourable Opinion