Eli Lilly and Company articles

Introduction

• MPS I is caused by a deficiency of the lysosomal enzyme a-L-iduronidase (IDUA) leading to GAG accumulation in multiple tissues and organs
• This accumulation results in a complex array of progressive, multi-systemic pathologies, including CNS manifestations
• Approved therapies include enzyme replacement therapy (ERT), with chaperone and gene therapies under investigation
• Treatment with approved E

Introduction

• Mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome) is caused by a deficiency of the lysosomal enzyme arylsulfatase B (ARSB)
• ARSB deficiency results in incomplete or blocked degradation of glucosaminoglycans (GAGs), which accumulate in the lysosome and disrupt normal cell function
• Disruption of cell function manifests in symptoms of MPS VI:
• Short stature, coarse facial features, stiff joints, breathin

• MPS I is caused by deficiency of the lysosomal enzyme a-L-iduronidase (IDUA) leading to GAG accumulation in multiple tissues and organs
• This accumulation results in a complex array of progressive, multi-systemic pathologies, including CNS manifestations
• Approved therapies include enzyme replacement therapy (ERT), with chaperone and gene therapies under investigation
• Treatment with approved ERT does not adequately address CNS manifestations

HYPOTHESIS: sustained therapeutic effect could be achieved by administration of IDUA-secreting allogeneic human cells shielded within spheres designed to avoid immune rejection and pericapsular fibrotic overgrowth (PFO)

Introduction

• Mucopolysaccharidosis type VI (MPS-6, Maroteaux-Lamy syndrome) is caused by a deficiency of the lysosomal enzyme arylsulfatase B (ARSB)
• ARSB deficiency results in incomplete or blocked degradation of glycosaminoglycans (GAGs), which accumulate in the lysosome and disrupt normal cell function
• Disruption of cell function manifests in symptoms of MPS-6:
• Short stature, coarse facial features, stiff joints, breathing