Fabry enzyme replacement therapy (ERT) based on mannose-mediated cellular uptake shows encouraging preclinical results that allow start of early clinical trials
Freiburg, Germany, August 27, 2015
Greenovation Biotech GmbH announced today that scientists at Baylor Institute, USA and Greenovation, Germany published results from a preclinical study in Fabry mice in the Journal of Inherited Metabolic Diseases. Results of the study imply that replacement enzymes exhibiting mannose-terminated glycosylation patterns are efficiently delivered to their subcellular targets, the lysosomes.
Lysosomal storage diseases (LSDs) like Fabry disease are caused by inborn absence of certain degradation enzymes, leading to continuous accumulation of problematic compounds in the cells. In Fabry patients, sphingolipid accumulation leads to various symptoms like e.g. excruciating pain, heart- and kidney failure. Enzyme replacement therapy (ERT) is a treatment option for several LSDs: Biopharmaceutical versions of the missing enzymes are intravenously infused. Once in the bloodstream, the compounds are taken up by cells either through the mannose 6-phosphate receptor (M6PR) or the mannose receptor (MR). It is generally believed that M6PR-mediated endocytosis is a key mechanism of ERT in treating patients with LSDs.
The encouraging results show that mannose receptor-mediated delivery of moss-made α-galactosidase A effectively corrects enzyme deficiency in Fabry mice. The enzymes exhibit mannose-terminated glycosylation patterns and act equally to mannose 6-phosphate-harboring enzymes in the treatment of Fabry disease and probably other lysosomal storage disorders in which non-macrophage cells are affected.
"We are very excited about the results of this preclinical study. The findings allow the start of early clinical trials that will investigate the effect of moss-aGal in humans suffering from Fabry disease," said Dr. Thomas Frischmuth, CEO.
However, the therapeutic efficacy of MR-mediated uptake of mannose-terminated enzymes in patients suffering from LSDs has not yet been fully evaluated. In the published study, scientists tested the effectiveness of non-phosphorylated α-galactosidase A produced in moss (referred to as moss-aGal) in vitro and Fabry mice. Endocytosis of moss-aGal was MR-dependent. Compared to agalsidase alfa, the current treatment option, moss-aGal was more efficiently targeted to kidney, whereas cellular localization of moss-aGal and agalsidase alfa in the heart was comparable. Clearance of accumulated substrate in heart and kidney by a single injection of moss-aGal was comparable to the effect of agalsidase alfa. These encouraging results allow now the start of early clinical testing.
Results of the study are freely accessible under
About Baylor Institute
Established in 1984 in Dallas, Texas, Baylor Research Institute (BRI) promotes and supports research to bring innovative treatments from the laboratory workbench to the patient bedside. To achieve this bench-to-bedside concept, BRI focuses on basic science, clinical trials, healthcare effectiveness and quality of care research. Today, BRI is conducting more than 930 active research protocols with 400 research investigators, spanning more than 22 medical specialties, and has research and development projects in areas ranging from human immunology and orphan metabolic diseases to diabetes, cardio-vascular disease and many other unmet medical needs.
About Greenovation Biotech GmbH
Greenovation develops plant made next generation therapeutics using its proprietary BryoTechnology platform. The core competency of the company is optimization and effective production of highly-efficient glycoproteins for the treatment of orphan diseases.
Greenovation is a privately owned biopharmaceutical company based in Heilbronn, Germany, that was founded in 1999 by Prof. Dr. Ralf Reski and Prof. Dr. Gunter Neuhaus. Today, Zukunftsfonds Heilbronn and L-EigenkapitalAgentur (Karlsruhe) are main owners of the Greenovation Biotech GmbH.