Mucopolysacharidosis Research Project

Mucopolysaccharidosis (MPS) is a group of lysosomal storage disorders (LSD) caused by a deficiency of the lysosomal-based enzymes that fail to metabolize glycoaminoglycans (GAG). Lysosome accumulation of GAG in many MPS causes hepatosplenomegaly, skeletal abnormalities, cardiac and pulmonary aberrations, connective tissue defects, ocular lesions and intellectual developmental disabilities. While enzyme replacement therapies (ERT) are the current mainstay for treating some MPS, it pose three significant limitations. First, ERT are expensive. Second, homozygotic mutation is associated with antibodies that can lead to drug resistance and immunological reactions. Third, ERT do not cross the blood-brain barrier (BBB).

The Institute is performing collaborative research to identify small molecules that would cross the BBB and reduce the high levels of accumulated GAG in the central nervous system (CNS).  This approach would offer three potential advantages over ERT to treat the CNS manifestations of MPS: 1) more effective crossing of the BBB; 2) decrease GAG levels in the CNS more universally; and 3) the treatment cost per patient would be substantially lower.

A key barrier to finding small molecules that could treat the CNS manifestations of MPS is a lack of a robust in vitro model that can more precisely identify and help optimize drug leads. A high-throughput, cell model of the BBB from MPS-specific induced pluripotent stem cells (iPSC) cells could remove this barrier.

The Institute co-developed a first-in-kind iPSC technology that is virus-free and oncogene-free that would provide the most accurate cell models of MPS patients for drug screening.

The Institute is currently developing a diverse biorepository of MPS-stem cell models for performing drug development.  The ultimate objective of this research is to apply stem cell technologies to develop cell models of the BBB from MPS patients for preclinical drug discovery.  MPS patients should sign up on our patient registry.  Patients selected to participate in the research will be asked to provide medical records to confirm their diagnosis and type of MPS mutation. Also, a tissue sample will be collected and shipped to the Institute for further processing.  The research represents a collaboration between the Institute, Cellular Engineering Technologies and the National Mucopolysacharidosis Society.

© 2019 John Paul II Medical Research Institute.