Roberto Giugliani, MD, PhD, Professor at the Department of Genetics of the Federal University of Rio Grande do Sul (UFRGS), Chief of the Medical Genetics Center of Hospital de Clinicas de Porto Alegre, and Director of the WHO Collaborating Centre for the Development of Medical Genetics Services in Latin America, discusses an ongoing phase 2 study to evaluate the safety and tolerability of pentosan polysulfate sodium (PPS) in subjects with mucopolysaccharidosis type VI (MPS VI). Information about this study was recently presented at WORLDSymposium 2022.
MPS VI is a progressive lysosomal storage disorder caused by the deficiency in N-acetylgalactosamine 4-sulfatase. This disease has a variable spectrum of symptoms. Neurological complications include clouded corneas, deafness, thickening of the dura, and pain caused by compressed or traumatized nerves and nerve roots. Growth is normal for the first few years of life but stops suddenly during the early school age years. By the age of 10, children have developed a shortened trunk, crouched stance, and restricted joint movement. In more severe cases, children also develop a protruding abdomen and forward-curving spine. Skeletal changes (particularly in the pelvic region) are progressive and limit movement. Many children also have umbilical or inguinal hernias. Nearly all children have some form of heart disease, usually involving valve dysfunction.
PPS is a semi-synthetic drug that mimics glycosaminoglycans (GAGs) which have a regulatory role in the body and interact with proteins involved in inflammation including the NF-κB pathway, the IL-1 pathway, and the NGF pathway. By regulating these pathways, PPS is able to decrease inflammation and pain.
As Dr. Giugliani explains, the phase 2 clinical trial is an ongoing double-blind placebo-controlled study to evaluate the safety and tolerability of PPS compared to placebo in patients with MPS VI who are receiving enzyme replacement therapy. Approximately 12 patients will receive weekly subcutaneous injections of PPS (1.0 mg/kg or 1.5 mg/kg depending on age), or placebo, for 24 weeks.
To learn more about MPS VI and other rare lysosomal storage disorders, visit https://checkrare.com/diseases/lysosomal-storage-disorders/