Mathias Schmidt, PhD, President and CEO of JCR Pharmaceuticals USA, discusses the mechanism of action of pabinafusp-alfa, an investigational therapy for mucopolysaccharidosis type II (MPS II; Hunter syndrome).
MPS II is a rare, progressive lysosomal disease caused by deficient activity of iduronate-2-sulfatase, attributable to pathogenic variants of the iduronate-2-sulfatase gene (IDS). This disease has a variable clinical presentation but common signs and symptoms include: developmental decline between 18 and 36 months, followed by progressive loss of skills; coarse facial features; skeletal irregularities; obstructive airway and respiratory complications; joint stiffness; retinal degeneration; and communicating hydrocephalus. Current standard of care is weekly intravenous infusions of idursulfase; however, this form of enzyme replacement therapy does not provide benefit for neuronopathic MPS II patients.
As Dr. Schmidt explains, pabinafusp alfa is an iduronate-2-sulfatase enzyme fused with anti-human transferrin receptor antibody. The antibody is designed to cross the blood-brain-barrier through transferrin receptor-mediated transcytosis, and its uptake into cells is mediated through the mannose-6-phosphate receptor. This allows the idursulfase attached to the antibody to pass the blood-brain-barrier, leading to enzyme uptake in various brain tissues and subsequently minimizing neurological symptoms in MPS II patients.
Previous clinical trials have provided positive results suggesting pabinafusp alfa is efficacious against both somatic and neurological symptoms. This data led to the approval of this drug in Japan.
To learn more about MPS II and other rare lysosomal storage disorders, visit https://checkrare.com/diseases/lysosomal-storage-disorders/
