Intrathecal enzyme replacement therapy has been proposed to treat central nervous system (CNS) disease due to mucopolysaccharidosis type I. Our research has shown that repeated injections of recombinant enzyme into the spinal fluid corrects enzyme deficiency and normalizes lysosomal storage in the canine model. The challenge is to translate the success in the animal where there are fewer study limitations to human patients where studies are more restricted. This review will explore what is known about the measurement of clinically-relevant outcomes of intrathecal enzyme replacement therapy for MPS I (including ongoing clinical trials), the challenges in translating therapies for the CNS in rare diseases, and new outcome measures that could aid translation of CNS therapies for MPS disorders.
Keywords: Enzyme replacement therapy, hurler, intrathecal, lysosomal storage disease, mucopolysaccharidosis, CNS, spinal fluid, clinically-relevant outcomes, MPS I, CNS therapies, MPS disorders, lysosomal hydrolase alpha-L-iduronidase, leukocyte enzymatic assays, hydrocephalus and spinal cord compression, ventriculoperitoneal shunt