Morquio syndrome, also known as mucopolysaccharidosis type IV (MPS-IV), is a rare inherited lysosomal storage disease caused by deficiency of the enzyme N-acetylgalactosamine 6-sulfatase (GALNS). This enzyme is responsible for breaking down glycosaminoglycans (GAGs), long chains of sugar molecules important for healthy cellular functioning. Without sufficient GALNS enzyme activity, GAGs accumulate abnormally in tissues and organs throughout the body. Over time, this buildup causes progressive damage and symptoms of the disease.
There are two primary types of Morquio syndrome - Morquio A (MPS IVA), caused by GALNS deficiency, and the extremely rare Morquio B (MPS IVB). Morquio A accounts for approximately 95% of all MPS IV cases. Symptoms tend to appear in early childhood and worsen with age. Common signs include skeletal abnormalities such as short stature, spinal deformities, flattened nasal bridge, protruding sternum, and joint stiffness. Other complications can include heart and respiratory issues, hearing loss, hernias, liver and spleen enlargement, and dental problems. While intelligence is unaffected, physical limitations reduce quality of life and life expectancy. Currently, there is no cure for Morquio Syndrome (MPS-IV) Drug and treatment focuses on managing symptoms.
New Therapies in Development
Considerable research efforts over the past decade aim to develop effective disease-modifying therapies for Morquio A. Enzyme replacement therapy (ERT) involves administering recombinant versions of the defective GALNS enzyme intravenously to facilitate uptake into cells. Vimizim (elosulfase alfa) was approved by the FDA in 2014 as the first ERT for Morquio Syndrome (MPS-IV) Drug. clinical trials found Vimizim significantly reduced urinary GAG levels in patients aged 5 and older with a manageable safety profile. However, there were limitations in achieving clinically meaningful outcomes related to skeletal abnormalities, motor function, and endurance.
More recently, the Phase 3 PERFECT and PERFECT Pediatric studies evaluated the efficacy and safety of vosoritide, a C-type natriuretic peptide analog, in children with Morquio A. Results published in 2021 showed vosoritide significantly increased annualized growth velocity versus placebo after one year of treatment. It also stabilized abnormalities in skeletal disproportion that worsen growth potential. These findings represent an important milestone, with vosoritide being the first drug to potentially address the root cause of skeletal dysplasia in Morquio A. Biomarin Pharmaceutical is seeking regulatory approval for vosoritide globally.
Another promising approach in development is gene therapy. Using modified viruses to deliver functioning GALNS genes directly into the body aims to restore enzyme production in tissues and cells. AVROBIO’s investigational gene therapy AVR-RD-02 achieved proof of concept in a Phase 1/2 trial. Four out of five pediatric patients demonstrated lowered urinary GAG levels. A larger Phase 2 trial is ongoing to further evaluate efficacy and safety of a single dose. Additionally, REGENXBIO is advancing RGN-929, an AAV9 gene therapy delivering GALNS, with plans to initiate pivotal studies this year. The potential for a one-time treatment that could correct the genetic basis of Morquio A raises hope for a disease-modifying therapy.
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