We have previously shown that glycosaminoglycan (GAG) storage in the mucopolysaccharidoses (MPS) leads to inflammation, a major contributor to the degenerative cartilage disease in MPS patients. We have also recently identified one FDA-approved drug, pentosan polysulfate (PPS), which resulted in remarkable clinical improvements in MPS VI rats. We compared the effect of oral, daily PPS administration to once weekly, subcutaneous (sc) injection in this animal model. The bioavailability of injected PPS is greater than oral, suggesting better delivery to difficult tissues such as bone and cartilage. Enhanced effects of sc treatment included greater endurance, better improvements in cartilage and bone and, most importantly, GAG reduction in urine, serum and tissues. Treating MPS patients with PPS is medically plausible given that the drug has been safely used in patients with other conditions for many years, and it addresses two key pathologic features – GAG storage and GAG-induced inflammation. The first clinical trial of PPS in MPS will begin this summer. However, despite these advances, the mechanism(s) leading to PPS-induced GAG reduction in MPS remain unknown, nor is it known if the findings in MPS VI extend to other MPS types. The current proposal is therefore focused on addressing these important questions.
– Calogera Simonaro, PhD
Icahn School of Medicine at Mount Sinai New York, NY