Biomarker kinetic study in children with MPSIH treated with HSCT
Research type
Research Study
Full title
Prospective study on temporal changes of biomarker kinetics in different compartments and their correlation with clinical outcomes in children with mucopolysaccharidosis IH (MPSIH) treated with haematopoietic stem cell transplantation
IRAS ID
226120
Contact name
Robert Wynn
Contact email
Sponsor organisation
Manchester University NHS Foundation Trust
Duration of Study in the UK
3 years, 1 months, 5 days
Research summary
Children with Hurler syndrome have too little of an enzyme called alpha-l-iduronidase, which normally breaks down substances called glycosaminoglycans (GAGs). These GAGs can build up in the cells of many body tissues, causing the physical problems and difficulties with development seen in children with Hurler syndrome. We can measure the GAGs in different tissues and in urine.
Most children with Hurler syndrome are treated with a bone marrow transplant (BMT). This involves children being given blood cells from a donor to make the missing enzyme. Donor blood cells are able to cross into the brain to provide missing enzyme to cease neurodegeneration.
We measure the amount of donor blood cells, blood enzyme and the urinary GAGs to indicate the success of BMT. We know that in the long term where the donor bloods cells work and make enzyme then the organs affected by Hurler syndrome are made better.
In this study we are trying to study the relationship between the donor enzyme levels and the GAGs and how much better the patient becomes after transplant. We are trying to see if those patients who have the best GAG level have the best outcome. We also wish to study the GAG level in different tissues.
It is recognised that there are no studies documenting the natural history of biomarkers, including IDUA production and substrate reduction, in human cerebrospinal fluid (CSF) after BMT. Changes in such biomarkers might be expected to occur before clinical changes and be able therefore to predict subsequent clinical events.
This study aims to study the temporal changes of these biomarkers in different body compartments in children undergoing BMT and to correlate those changes with subsequent clinical outcomes. Such biomarkers might help us to develop new treatment strategies to improve the neurocognitive outcome in children with Hurler Syndrome.REC name
North West - Greater Manchester Central Research Ethics Committee
REC reference
17/NW/0653
Date of REC Opinion
14 Feb 2018
REC opinion
Further Information Favourable Opinion