dc.contributor.author |
Hennermann, Julia B |
|
dc.contributor.author |
Arash-Kaps, Laila |
|
dc.contributor.author |
Fekete, György |
|
dc.contributor.author |
Schaaf, Andreas |
|
dc.contributor.author |
Busch, Andreas |
|
dc.contributor.author |
Frischmuth, Thomas |
|
dc.date.accessioned |
2020-03-27T11:56:00Z |
|
dc.date.available |
2020-03-27T11:56:00Z |
|
dc.date.issued |
2019 |
|
dc.identifier.citation |
journalVolume=42;journalIssueNumber=3;journalTitle=JOURNAL OF INHERITED METABOLIC DISEASE;pagerange=527-533;journalAbbreviatedTitle=J INHERIT METAB DIS; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/7483 |
|
dc.identifier.uri |
doi:10.1002/jimd.12052 |
|
dc.description.abstract |
Moss-aGalactosidase A (moss-aGal) is a moss-derived version of human α-galactosidase developed for enzyme replacement therapy in patients with Fabry disease. It exhibits a homogenous N-glycosylation profile with >90% mannose-terminated glycans. In contrast to mammalian cell produced α-galactosidase, moss-aGal does not rely on mannose-6-phosphate receptor mediated endocytosis but targets the mannose receptor for tissue uptake. We conducted a phase 1 clinical trial with moss-aGal in six patients with confirmed diagnosis of Fabry disease during a 28-day schedule. All patients received a single dose of 0.2 mg/kg moss-aGal by i.v.-infusion. Primary endpoints of the trial were safety and pharmacokinetics; secondary endpoints were pharmacodynamics by analyzing urine and plasma Gb3 and lyso-Gb3 concentrations. In all patients, the administered single dose was well tolerated. No safety issues were observed. Pharmacokinetic data revealed a stable nonlinear profile with a short plasma half-life of moss-aGal of 14 minutes. After one single dose of moss-aGal, urinary Gb3 concentrations decreased up to 23% 7 days and up to 60% 28 days post-dose. Plasma concentrations of lyso-Gb3 decreased by 3.8% and of Gb3 by 11% 28 days post-dose. These data reveal that a single dose of moss-aGal was safe, well tolerated, and led to a prolonged reduction of Gb3 excretion. As previously shown, moss-aGal is taken up via the mannose receptor, which is expressed on macrophages but also on endothelial and kidney cells. Thus, these data indicate that moss-aGal may target kidney cells. After these promising results, phase 2/3 clinical trials are in preparation. |
|
dc.format.extent |
527-533 |
|
dc.relation.ispartof |
urn:issn:0141-8955 |
|
dc.title |
Pharmacokinetics, pharmacodynamics, and safety of moss-aGalactosidase A in patients with Fabry disease |
|
dc.type |
Journal Article |
|
dc.date.updated |
2019-08-16T06:32:01Z |
|
dc.language.rfc3066 |
en |
|
dc.rights.holder |
NULL |
|
dc.identifier.mtmt |
30432380 |
|
dc.identifier.pubmed |
30746723 |
|
dc.contributor.department |
SE/AOK/K/II. Sz. Gyermekgyógyászati Klinika |
|
dc.contributor.institution |
Semmelweis Egyetem |
|