Results from a phase 2 trial of a blood-brain barrier penetrating enzyme (JR-141) in patients with MPS II in Brazil. Giugliani, R., Martins, A., M., Zambrano, M., Poswar, F., de Boer, A., P., Sato, Y., Tanizawa, K., Yamamoto, T., So, S., Yamaoka, M., & Kobayashi, M. Molecular Genetics and Metabolism, 129(2):S63, 2, 2020. ![Results from a phase 2 trial of a blood-brain barrier penetrating enzyme (JR-141) in patients with MPS II in Brazil [link]](https://bibbase.org/img/filetypes/link.svg "link")
Website doi abstract bibtex Mucopolysaccharidosis type II (MPS II, Hunter disease) is a rare, X-linked lysosomal disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene. The current intravenous enzyme replacement therapy (ERT) does not cross the blood-brain barrier (BBB) and cannot address central nervous system (CNS) manifestations of the disease, thus a novel therapy effective for the CNS is needed. Intrathecal and intracerebroventricular ERT administration are being tested, but these are invasive alternatives. JR-141 is a fusion protein that consists of human IDS and anti-human transferrin receptor antibody, designed to penetrate the BBB. Here we present the results of a phase 2, open-label, randomized, parallel group study to evaluate safety and efficacy of JR-141. Twenty patients, including 7 naive patients without previous ERT, were enrolled and received weekly intravenous infusions of 1.0, 2.0, or 4.0 mg/kg JR-141 for 6 months. The heparan sulfate (HS) concentrations in cerebrospinal fluid decreased at week 13 and 26 from baseline, indicating the penetration of JR-141 through BBB. Cognitive function and adaptive behavior were stable or improved in some patients during the study. The positive systemic effects of JR-141 were also demonstrated by some parameters, e.g. the concentrations of glycosaminoglycans in serum and urine, and the liver and spleen volumes. Some patients presented infusion-associated reactions, none of which were severe. No patients discontinued the study due to the drug-related adverse events. Taken together, the treatment of MPS II patients with JR-141 was well tolerated up to 4.0 mg/kg/week, the intravenous administered drug was able to decrease the levels of HS in the CSF, and several efficacy signals were detected. All subjects who completed this study have been enrolled in the extension study, which will provide longitudinal data and further information on the effects of JR-141.
Copyright © 2019
@article{
title = {Results from a phase 2 trial of a blood-brain barrier penetrating enzyme (JR-141) in patients with MPS II in Brazil},
type = {article},
year = {2020},
pages = {S63},
volume = {129},
websites = {https://linkinghub.elsevier.com/retrieve/pii/S1096719219309916},
month = {2},
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created = {2020-02-15T13:13:01.381Z},
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last_modified = {2021-10-19T17:30:54.223Z},
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abstract = {Mucopolysaccharidosis type II (MPS II, Hunter disease) is a rare, X-linked lysosomal disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene. The current intravenous enzyme replacement therapy (ERT) does not cross the blood-brain barrier (BBB) and cannot address central nervous system (CNS) manifestations of the disease, thus a novel therapy effective for the CNS is needed. Intrathecal and intracerebroventricular ERT administration are being tested, but these are invasive alternatives. JR-141 is a fusion protein that consists of human IDS and anti-human transferrin receptor antibody, designed to penetrate the BBB. Here we present the results of a phase 2, open-label, randomized, parallel group study to evaluate safety and efficacy of JR-141. Twenty patients, including 7 naive patients without previous ERT, were enrolled and received weekly intravenous infusions of 1.0, 2.0, or 4.0 mg/kg JR-141 for 6 months. The heparan sulfate (HS) concentrations in cerebrospinal fluid decreased at week 13 and 26 from baseline, indicating the penetration of JR-141 through BBB. Cognitive function and adaptive behavior were stable or improved in some patients during the study. The positive systemic effects of JR-141 were also demonstrated by some parameters, e.g. the concentrations of glycosaminoglycans in serum and urine, and the liver and spleen volumes. Some patients presented infusion-associated reactions, none of which were severe. No patients discontinued the study due to the drug-related adverse events. Taken together, the treatment of MPS II patients with JR-141 was well tolerated up to 4.0 mg/kg/week, the intravenous administered drug was able to decrease the levels of HS in the CSF, and several efficacy signals were detected. All subjects who completed this study have been enrolled in the extension study, which will provide longitudinal data and further information on the effects of JR-141.<br/>Copyright © 2019},
bibtype = {article},
author = {Giugliani, Roberto and Martins, Ana Maria and Zambrano, Marina and Poswar, Fabiano and de Boer, Ana Paula and Sato, Yuji and Tanizawa, Kazunori and Yamamoto, Tatsuyoshi and So, Sairei and Yamaoka, Mariko and Kobayashi, Minako},
doi = {10.1016/j.ymgme.2019.11.147},
journal = {Molecular Genetics and Metabolism},
number = {2}
}
Downloads: 0
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