Paradigm Biopharmaceuticals Ltd. announced an abstract on Paradigm's phase 2 clinical trial evaluating injectable Pentosan Polysulfate Sodium (iPPS) against placebo in mucopolysaccharidosis type VI (MPS-VI) patients has been accepted for a poster presentation at the WORLDSymposium in 2023. The WORLDSymposium is the annual research conference focused on new therapies for lysosomal storage diseases, such as MPS-VI. The 19th annual WORLDSymposium conference will be held in Orlando, Florida on February 22-26, 2023. Dr. Roberto Giugliani MD, PhD, MSc, the Principal Investigator of Paradigm's phase 2 clinical trial, will be presenting the poster, which provides an update on the enrolment and baseline characteristics of MPS-VI participants in the trial. Brazil has one of the largest populations of MPS-VI patients globally (1), thus researchers are evaluating the use of Paradigm's iPPS to treat MPS-VI patients in this phase 2 study based in Brazil. The study is randomised, double-blind, and placebo-controlled to evaluate the safety and tolerability of iPPS in patients with MPS-VI. According to the study protocol, approximately 12 patients will be randomised 2:1 to receive iPPS or placebo. Participants are dosed weekly for 24 weeks with the primary endpoint being safety. The secondary endpoints are improvements in
pain and function. IPPS is a non-opioid subcutaneous injectable with the potential to treat residual musculoskeletal symptoms in MPS as an adjunct therapy to current standards of care. Previous studies have shown iPPS improves pain and function in patients with MPS-I, MPS-II and MPS-VI (2­4). Mucopolysaccharidoses belong to a group of more than 70 inherited lysosomal storage diseases (5). Lysosomes are the recycling centres of all cells that break down excess or worn-out cell parts with their digestive enzymes. Mucopolysaccharidosis disorders are due to errors with one of the
enzymes that break down and recycle glycosaminoglycans (GAGs). As these waste products cannot be eliminated, they accumulate within the lysosomes of virtually every type of cell in the body, causing cells, tissues, and organs to function abnormally, leading to progressive damage.
The heart, bones, joints, respiratory system, and central nervous system, including cognitive function in most cases, may eventually be affected. Symptoms are not generally apparent at birth but emerge gradually as a result of defective lysosomal storage and resulting cell damage over
time (6­8). Eleven different types of mucopolysaccharidosis have been described, where each is the result of a deficiency in one of the enzymes in the glycosaminoglycan degradation pathway (9). Mucopolysaccharidosis type VI, also known as Maroteaux-Lamy syndrome, is an ultra-rare
autosomal recessive lysosomal storage disorder that affects between 0.36 and 1.30 of every 100,000 live births (6). It results in the development of multisystem clinical manifestations. Mucopolysaccharidosis type VI disorders caused by variations (mutations) in the ARSB gene for the enzyme arylsulfatase B range from very slowly to rapidly progressing, depending on the specific disease-causing mutation (10). The life expectancy of people with MPS-VI depends on symptom severity, and severely affected individuals may survive only until late childhood or adolescence without treatment. Although life expectancy may be reduced, those with milder forms often live into adulthood. Heart disease and airway obstruction are major causes of death in individuals with MPS-VI (11,12). Current treatments for MPS-VI patients include enzyme replacement therapy, however MPS-VI
patients undergoing this therapy continue to report ongoing stiffness, pain, and inflammation which impacts their activities of daily living. The current standards of care are not adequate in treating the pain associated with joint inflammation and musculoskeletal issues.