Novel diagnostic biomarker reference standards for newborn screening of Mucopolysaccharidoses type I and II.

Project Summary The goal of this project is to design and prepare diagnostic biomarker reference standards for the endogenous glycosaminoglycan (GAG) Mucopolysaccharidosis type I (MPS-I) and type II (MPS- II) biomarkers. MPS-I and MPS-II are lysosomal storage disorders (LSDs) which are listed on the Recommended Uniform Screening Panel (RUSP) in the United States and are included in global Newborn Screening (NBS) programs and Pilot studies currently ongoing. One issue with the first- tier enzyme activity screening is the high prevalence of false positives, which may be eliminated by second-tier biomarker screening. The endogenous GAG biomarker method has been shown in recent studies to provide accurate discrimination of diagnosed newborns from the reference range of healthy newborns and newborns with pseudodeficiencies (for MPS-II). Additionally, by this method unique biomarkers have been identified for each disease, which will aid diagnostic labs in clinical evaluation. Currently, no chemically identical, quantified reference standards (which meets recommendations from FDA guidance on bioanalytical method validation) are available on the market. The GAG disaccharide internal standards prepared within the scope of this project will meet the reference standard recommendations indicated by the FDA, which are not currently met by any other product on the market. As a result, GelbChem will be the first supplier of all materials needed to complete bioanalytical validation of the endogenous GAG biomarker method for MPS-I and MPS-II.