Understanding the nature of inhibitors in haemophilia
Research type
Research Study
Full title
Understanding the nature of inhibitors in haemophilia
IRAS ID
184327
Contact name
Vania Coelho
Contact email
Sponsor organisation
University College London
Clinicaltrials.gov Identifier
Z6364106/2015/07/19, UCL Data Protection Registration; 15H14, Great Ormond Street NHS Research and Development; 9510, Royal Free London NHS Research and Development
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Haemophilia A (HA) is a bleeding disorder involving a deficiency of Factor VIII (FVIII), a clotting protein.
The standard treatment of HA is the replacement of the missing clotting factor by injections of FVIII preparations. Infusions of the replacement FVIII are mostly effective however some patients develop a type of antibody called “inhibitors” which make the FVIII treatment ineffective. Inhibitors appear because the body recognises the FVIII concentrates as a “foreign” protein and tries to destroy them.
Patients who develop inhibitors may undergo “Immune Tolerance Induction” (ITI) treatment. This treatment requires frequent, intravenous infusion of FVIII, which is invasive and demanding especially as the treatment can last for approximately 9 months. It is not guaranteed that the treatment will work with failure rates of approximately 20% and it is also not possible to predict with confidence which patients will respond to treatment.
The cells that lead to the production of inhibitors are called B-cells. After first contact with FVIII, these cells may turn into “FVIII-memory B-cells”, and become specialized in quickly recognising the FVIII and producing the inhibitor.
We think that patients with inhibitors share a specific genomic identity within their DNA which we hope to exploit to (1) identify patients at risk of inhibitor formation and (2) predict the clinical outcome of the ITI. This may enable us to develop a test for those who are unlikely to respond soon after starting ITI and potentially move them onto alternative treatment approaches to improve the chances of eradicating intractable inhibitors as these patients have a reduced life expectancy.REC name
London - Bloomsbury Research Ethics Committee
REC reference
15/LO/1372
Date of REC Opinion
22 Oct 2015
REC opinion
Further Information Favourable Opinion