Moss-aGal proven effective and safe
in Phase I clinical trial
The first biopharmaceutical ever produced in moss, Greenovation’s moss-aGal, was successfully tested in a Phase I clinical trial (October 2017). Six female patients suffering from a rare genetic lysosomal storage disorder, Fabry disease, tolerated the treatment very well.
Fabry disease is characterized by deficient activity of alpha-galactosidase that Greenovation’s moss-aGal aims to replace. A single injection of moss-aGal led to significant decrease of Gb3 levels 14 and 28 days post administration, that indicates an efficient targeting of moss-aGal to the kidneys of the patients – one of the most affected organs.
The data were presented at the 14th World Symposium™ for Lysosomal Storage Diseases in San Diego, USA, by Prof. Julia Hennermann, University Medical Center Mainz.
Moss-aGal is a recombinant form of human alpha-galactosidase produced in moss (physcomitrella patens) using Greenovation’s BryoTechnology®. Expression in moss creates a protein that is identical to the human protein with customized glycosylation pattern. The production is free of human pathogens and animal compounds.
The plans for a clinical trial II/III are already in progress.
One dose group with 6 patients: 0.2 mg/kg i. v.; single dose; clinical schedule of 28 days
Secondary (exploratory) endpoints:
- Efficacy (Gb3/lyso-Gb3 levels in plasma and urine
For detailed study information, please visit www.clinicaltrialsregister.eu, EudrCT-No.: 2014-004325-40.
This product is in clinical trial and is not available for therapy.
Moss-aGal for patients suffering
from Fabry Disease
Moss-aGal will be the first enzyme replacement treatment of Fabry disease produced in moss that exhibits optimized N-glycosylation patterns of the protein alpha-galactosidase A. Studies in mice show that this translates into enhanced cellular uptake and favourable organ distribution.
Fabry disease is a rare genetic lysosomal storage disorder that is caused by deficient activity – subnormal or absent – of the lysosomal enzyme α-galactosidase A. Absence of the enzyme leads to progressive accumulation of glycosphingolipids, predominantly ceramide trihexoside (CTH or Gb3), in most tissues and cell types, particularly the vascular endothelial and smooth-muscle cells leading to various symptoms including excruciating pain, ischaemia and infarction. Fabry disease affects about 1–5 in 10,000 people worldwide.
Moss-aGal: enhanced cellular uptake into the target organ kidney
Being an enzyme replacement therapy, moss-aGal replaces the missing or reduced activity of the lysosomal enzyme alpha-galactosidase A in patients with Fabry disease. The kidney and heart are the organs most affected by the disease. Compared with other replacement therapies, the mannose receptor-mediated uptake of moss-aGal leads to an increased uptake of the enzyme in the kidney in mice. This has the potential for substantial improvements to patients’ quality of life.
Moss-aGal exhibits inherent N-glycan homogeneity
Treatment of Fabry disease is done by regular infusion of biotechnologically produced substitute of the missing enzyme, so called enzyme replacement therapy (ERT). The uptake of the infused enzyme into target cells from the bloodstream is mediated by glycan receptors. Therefore N-glycosylation, its pattern and homogeneity are key to the therapeutic efficacy of recombinant variants of the enzyme in treatment of Fabry disease.
Approved substitute enzymes are manufactured in mammalian cell lines (CHO or human fibroblast cells) exhibiting remarkable heterogeneity in N-glycosylation with only a minor fraction being relevant for target cell uptake.
Moss-aGal is manufactured in the moss system Physcomitrella patens and therefore benefits from the inherent N-glycan homogeneity of these organisms. Regarding its amino acid sequence moss-aGal is identical to the human enzyme. It could be demonstrated that over 95 % of the moss N-glycans are relevant for targeted uptake of the biopharmaceutical product into the cell.