Intrathecal enzyme therapy for mucopolysaccharidosis I

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DESCRIPTION (provided by applicant): Mucopolysaccharidosis I (MRS I) is a lysosomal storage disorder due to deficiency of the enzyme alpha-L- iduronidase. Enzyme replacement therapy with recombinant human alpha-L-iduronidase (laronidase, Aldurazyme) has been developed and helps many physical ailments of the disease. However, the enzyme replacement therapy cannot treat disease of the brain or spinal cord, because the therapy cannot penetrate the blood-brain barrier to access those areas. Giving the enzyme directly into the spinal fluid (intrathecally) may provide a straightforward way to deliver the treatment to the brain and spinal cord, which could help many patients with MRS I. Dogs with the canine model of MRS I receiving intrathecal injections of iduronidase achieve supranormal concentrations of iduronidase in CNS tissues and have dramatic improvement in their lysosomal storage. In the first part of this project, intrathecal enzyme replacement therapy is further studied in dogs, for dose optimization, validation of non-invasive methods of judging the success of the treatment, and use in the very young. The second part of the project involves the translation of the preclinical work in dogs to a clinical trial in MRS I patients. Intrathecal enzyme therapy will be studied in patients with spinal cord compression, which is a debilitating condition common in MRS I patients that often requires spinal surgery to correct. This research investigates intrathecal enzyme therapy for canine MRS I with translation to the first clinical trial of intrathecal enzyme replacement therapy for MRS I patients.