Simple test for mucopolysaccharidoses biomarkers developed
MedWire News: Scientists have developed a simple biomarker-based diagnostic test for mucopolysaccharidoses (MPS), a group of autosomal recessive inherited metabolic disorders.
Several treatments, including enzyme replacement therapy and hematopoietic stem cell transplantation, are available for treatment of the 11 forms of MPS, but their success depends on how quickly the disease is diagnosed and treated.
"The typical time from seeing first symptoms to diagnosis of MPS is about 3 years. Since the early signs of disease are common childhood issues like ear infections and learning disorders, the disease is usually not immediately recognized," explained study author Jeffrey Esko from the University of California San Diego, USA, in a press statement.
"A child often has multiple visits with their pediatrician. Eventually they are referred to a metabolic disease specialist, where rare diseases are considered. It takes an expert to identify MPS and its most likely form in each patient. Every subclass of MPS has its own specific diagnostic test, so developing better diagnostics is an essential part of effective treatment."
Glycosaminoglycans or mucopolysaccharides accumulate in the cells, blood, and urine of individuals with MPS. Esko and team created a test to target the nonreducing ends of these carbohydrates.
The test enzymatically depolarizes mucopolysaccharides releasing mono-, di-, or trisaccharides from their nonreducing ends.
The composition of the released mono- and oligosaccharides depends on the type of MPS that the patient has and can therefore be used diagnostically.
Liquid chromatography-mass spectrometry was used to assess amounts and types of biomarkers present in samples taken from people with different forms of MPS.
Esko and team believe that this technology could also be used to monitor the efficacy of MPS treatments, such as enzyme replacement therapy. A commercial diagnostic assay is currently being developed for this purpose, and to allow newborn screening and differentiation of different MPS types from blood and urine samples.
"Since the severity of the disease is highly variable among patients, this could provide a tool that a doctor can use to optimize dosing or treatment," said co-author Brett Crawford from Zacharon Pharmaceuticals, Inc., San Diego, California, USA. "Currently, all patients are treated with the same dose of drug."
The researchers suggest that the test could be used to find new forms of MPS and to refine definitions of the existing types.
The results of this study are published in the journal Nature Chemical Biology.
By Helen Albert