Iduronate-2-sulfatase fused with anti-hTfR antibody, pabinafusp alfa, for MPS-II : a phase 2 trial in Brazil
dc.contributor.author | Giugliani, Roberto | pt_BR |
dc.contributor.author | Martins, Ana Maria (Medicina) | pt_BR |
dc.contributor.author | So, Sairei | pt_BR |
dc.contributor.author | Yamamoto, Tatsuyoshi | pt_BR |
dc.contributor.author | Yamaoka, Mariko | pt_BR |
dc.contributor.author | Ikeda, Toshiaki | pt_BR |
dc.contributor.author | Tanizawa, Kazunori | pt_BR |
dc.contributor.author | Sonoda, Hiroyuki | pt_BR |
dc.contributor.author | Schmidt, Mathias | pt_BR |
dc.contributor.author | Sato, Yuji | pt_BR |
dc.date.accessioned | 2022-01-27T04:33:10Z | pt_BR |
dc.date.issued | 2021 | pt_BR |
dc.identifier.issn | 1525-0016 | pt_BR |
dc.identifier.uri | http://hdl.handle.net/10183/234518 | pt_BR |
dc.description.abstract | In Hunter syndrome (mucopolysaccharidosis II [MPS-II]),systemic accumulation of glycosaminoglycans (GAGs) dueto a deficiency of iduronate-2-sulfatase (IDS), caused by mu-tations in theIDSgene, leads to multiple somatic manifesta-tions and in patients with the severe (neuronopathic)phenotype, also to central nervous system (CNS) involve-ment. These symptoms cannot be effectively treated withcurrent enzyme-replacement therapies, as they are unableto cross the blood-brain barrier (BBB). Pabinafusp alfa, anovel IDS fused with an anti-human transferrin receptorantibody, was shown to penetrate the BBB and to addressneurodegeneration in preclinical studies. Subsequent phase1/2 and 2/3 clinical studies in Japan have shown markedreduction of GAG accumulation in the cerebrospinalfluid(CSF), along with favorable clinical responses. A 26-week,open-label, randomized, parallel-group phase 2 study wasconducted in Brazil to further evaluate the safety and efficacyof intravenously administered pabinafusp alfa at 1.0, 2.0,and 4.0 mg/kg/week in MPS-II patients. The safety profilesin the three dosage groups were similar. Neurodevelopmentalevaluation suggested positive neurocognitive signals despite arelatively short study period. The 2.0-mg/kg group, whichdemonstrated marked reductions in substrate concentrationsin the CSF, serum, and urine, was considered to provide thebest combination regarding safety and efficacy signals. | en |
dc.format.mimetype | application/pdf | pt_BR |
dc.language.iso | eng | pt_BR |
dc.relation.ispartof | Molecular therapy : the journal of the American Society of Gene Therapy. San Diego. Vol. 29, no. 7 (2021), p. 2378-2386. | pt_BR |
dc.rights | Open Access | en |
dc.subject | Mucopolissacaridose II | pt_BR |
dc.subject | Mucopolysaccharidosis II | en |
dc.subject | Hunter syndrome | en |
dc.subject | Iduronato sulfatase | pt_BR |
dc.subject | Disfunção cognitiva | pt_BR |
dc.subject | Pabinafusp alfa | en |
dc.subject | Heparitina sulfato | pt_BR |
dc.subject | JR-141 | en |
dc.subject | Blood-brain barrier | en |
dc.subject | Terapia de reposição de enzimas | pt_BR |
dc.subject | Iduronate-2-sulfatase | en |
dc.subject | Neurocognitive impairment | en |
dc.subject | Anti-human transferrin receptor antibody | en |
dc.subject | Heparan sulfate | en |
dc.subject | Enzyme-replacement therapy | en |
dc.title | Iduronate-2-sulfatase fused with anti-hTfR antibody, pabinafusp alfa, for MPS-II : a phase 2 trial in Brazil | pt_BR |
dc.type | Artigo de periódico | pt_BR |
dc.identifier.nrb | 001135970 | pt_BR |
dc.type.origin | Estrangeiro | pt_BR |
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