This technology includes the identification and use of a combination therapy consisting of human recombinant N-acetylgalactosamine-6-sulfate sulfatase (hrGALNS) and the pharmacological chaperone compounds Ezetimibe and Pranlukast for the treatment of Mucopolysaccharidosis Type IVA (MPS IVA). MPS IVA is a rare disease caused by mutations in the gene encoding the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Currently, hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) are available for patients with MPS IVA. This technology includes the combinatorial use of hrGALNS and pharmacological chaperon compounds Ezetimibe and Pranlukast that have been found to have an additive/synergistic effect in reducing enlarged lysosomes in MPS IVA patient cells.
The pharmacological chaperone compounds Ezetimibe and Pranlukast increase the activity of hrGALNS by a directly binding to it and stabilizing the protein structure. Therefore, these chaperone compounds can reduce the dose of hrGALNS needed for ERT when the two are used in a combination therapy.