Dr. Raymond Wang, M.D.

 Preclinical Phase of Intra-articular ERT for MPS1 A Complete Success!

We are very pleased to report that the preclinical phase of an in-depth Research Study, examining the delivery of enzyme directly into joint spaces to directly treat tissues damaged by MPS1, was a clear success!

Overview:

Funded by a grant from the MPS1 Research Foundation and CHOC Children’s Pediatric Subspecialty Faculty Group, this important project also received the support of Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center and Genzyme Corporation. Conducted by Dr. Raymond Wang, M.D., Dr. Afshin Aminian, M.D., and Dr. Patti Dickson, M.D., iduronidase enzyme was injected directly into the joints of dogs with MPS1 to determine both the safety and effectiveness of a potential new treatment for people suffering from MPS1.

Both stem cell/bone marrow transplantation and intravenous enzyme replacement therapy (ERT) with iduronidase have already been approved by the FDA for individuals with MPS1. While these treatments have revolutionized the lives of people with MPS I, neither can effectively deliver the needed enzyme into cartilage and joints because of the lack of blood vessels in those tissues. Consequently, progressive joint degeneration, cervical spinal cord stenosis, spinal kyphosis, hip dysplasia, and restriction of joint mobility continue in people with MPS1 even after treatment, causing drastic impairment of quality of life. Patients with MPS I must endure continued orthopedic surgeries, physical & occupational therapy, and pain due to these complications.

Background Information:

Planning for this carefully designed study began in 2010 and the first injections were performed on March 21, 2011. Each dog received the same dose of iduronidase in their right elbow and right knee joints. The left elbow and left knee joints did not receive the enzyme and were designated as the control for the study. All of the dogs received injections every month for six months. In all cases, the injections went smoothly and the dogs quickly resumed their normal level of activity. Unfortunately, the dogs’ overall MPS1 condition progressed (as expected) and they needed to be put to sleep at 18 months. At the conclusion of the study, a detailed microscopic analysis of the joint tissue was conducted.

Purpose:

The purpose of this "preclinical" phase of this study was to see if iduronidase injected into the joints (“Intra-articular ERT”) of dogs with MPS1 would be (a) safe and well-tolerated, and (b) successful in reducing GAG storage in joint tissue.

Study Results:

The results were clearly successful in both areas! There were no complications associated with injections. All dogs recovered and were up and walking within 30 to 60 minutes of the procedure. There was no joint swelling, stiffness, fevers, or refusal to walk post-procedure. Blood testing showed no significant abnormalities. Analysis of the joint showed dramatically successful reductions and eliminations of both chondrocyte and synoviocyte GAG storage in the treated joints. The injections successfully reduced or eliminated inflammatory cells and other markers of inflammation in the treated joints when compared to the non-treated joints.

Next Steps:

With the clear success of this Preclinical Study, the goal is to fund a FDA-approved phase I/II open-label clinical trial which will use intra-articular enzyme replacement therapy in human patients with MPS1 to determine if the iduronidase treatment is well-tolerated and effective to prevent further joint damage. Planned enrollment will be five patients for this study, to receive intra-articular iduronidase for 6 - 12 months; anticipated costs of the study will be quite significant, so we thank you again for your support as we endeavor to cure this serious need faced by all patients with MPS1.