Cross sectional biomarker kinetic study in children with MPS
Research type
Research Study
Full title
Cross sectional study on biomarkers in different compartments, multi-parametric MRI brain and their correlation with somatic manifestation and neurocognitive outcome in children with mucopolysaccharidoses
IRAS ID
228306
Contact name
Robert Wynn
Contact email
Sponsor organisation
Manchester University NHS Foundation Trust
Duration of Study in the UK
3 years, 2 months, 30 days
Research summary
Mucopolysaccharidoses (MPS) are a rare group of inherited lysosomal storage disorders with an estimated incidence of 1 in 20,000 live births. The MPS disorders result in serious multi-systemic disease, including cardiopulmonary complications, neurocognitive disabilities, skeletal deformities, visual and hearing defects. Premature death in untreated children is largely to life-threatening cardiopulmonary complications. The neurological effects of MPS inevitably lead to poor quality of life.
The treatment for MPS was symptomatic supportive care and palliative therapy until the first haematopoietic stem cell transplant (HSCT) in 1980 and the introduction of pharmacological enzyme replacement therapy (ERT) in 2003. These therapies provide the missing enzyme thereby preventing accumulation of GAGs and deterioration of organ functions. By altering the natural history of MPS using these two disease-modifying specific therapies, the life expectancy and quality of life of children with MPS have improved in the past two decades. The success of these therapies is closely related to the age of start therapy and the amount enzyme delivered by specific therapy.
Currently the disease outcomes (including organ, neurocognitive and functional outcomes) in these children treated with various therapies are mainly measured using clinical parameters. There are few studies objectively documenting the biomarkers, including enzyme level and substrate concentration, in human CSF and bone in these children. This study aims to study these biomarkers in different body compartments in these children and to correlate those changes with their clinical features. Multi-parametric MRI will be studied as a surrogate marker to correlate with the CSF substrate reduction. Such biomarkers might become endpoints of newer therapies such as our early-phase clinical gene therapy programmes in lysosomal storage disorders.REC name
North West - Greater Manchester Central Research Ethics Committee
REC reference
17/NW/0652
Date of REC Opinion
14 Feb 2018
REC opinion
Further Information Favourable Opinion