Using a mouse model, Heidelberg University Hospital researchers have for the first time successfully treated a severe congenital disorder in which sugar metabolism is disturbed. The team headed by Prof. Christian Körner, group leader at the Center for Child and Adolescent Medicine, demonstrated that if female mice are given mannose with their drinking water prior to mating and during pregnancy, their offspring will develop normally even if they carry the genetic mutation for the congenital disorder. The team’s outstanding work will contribute to better understanding of the molecular processes of this metabolic disease, along with the key stages in embryonic development, and may offer a therapeutic approach for the first time.
The Heidelberg-based researchers also collaborated with colleagues working with Prof. Hermann-Josef Gröne of the German Cancer Research Center (DKFZ)’s Division of Cellular and Molecular Pathology in Heidelberg. Their results have now been published online in the internationally respected journal Nature Medicine in advance of their publication in the print edition.
Rare disease: Approx. 1,000 children affected
So far 1,000 children worldwide are affected by congenital disorders of glycosylation (CDG), which are classified as rare diseases. Affecting around 800 children, type CDG-Ia is most frequent. The number of unreported cases is high, however. Children with CDG are severely physically and mentally disabled, with approx. 20 percent dying before the age of two. To date, no therapy has been available to treat the disorder.
CDG-Ia is caused by mutations in the genetic information for the enzyme Phosphomannomutase 2 which is involved in important glycosylation processes: Mannose-1-phosphate is not produced in sufficient quantities. As a result, glycosylation malfunctions, meaning that sugar chains that normally aid in form, stability and function of the glycoproteins are not completely attached to the body’s proteins or in some cases, are not attached at all. The lack of oligosaccharide chains leads to impairment of neurological, growth and organ development. The disorder only manifests if the baby inherits a mutated gene from both the mother and the father. The parents, who each carry one mutated and one “healthy” copy of the gene, do not exhibit any symptoms.
Mice take up mannose in drinking water
The mouse model developed by Prof. Körner and his team is characterized by mutations in the Phosphomannomutase 2 gene and demonstrates reduced enzyme activity, comparable to CDG-Ia in man. In their current study, the scientists exploited the ability of mannose to cross the placental barrier. This means that if the pregnant mouse takes up mannose, it also reaches the embryos in the uterus.
“One week prior to mating, we began giving the female mice mannose with their drinking water,” explained biochemist Prof. Körner. The additional mannose supply up to birth increased the mannose levels in the embryos’ blood. “The mice were born without defects and also after they were born, developed without any symptoms of the disorder, even if they no longer took up any mannose,” Körner added. The successful studies performed by the Heidelberg University Hospital researchers clearly show the key role played by the supply of proteins with sugar chains during embryonic development.
New therapeutic approach
“Clinical studies in the U.S. and Germany have already been performed in which children with CDG-Ia were given mannose after they were born, either orally or by intravenous infusion. Unfortunately, these attempts have not been successful,” explained Dr. Christian Thiel, head of the laboratory. “This means that the critical point at which it is possible to influence development must be during development in the uterus.” For women with a risk of CDG-Ia, administering mannose during pregnancy may serve as a new therapeutic approach.
Heidelberg University Hospital’s Center for Child and Adolescent Medicine (Managing Director: Prof. Georg F. Hoffmann) is one of the world’s top centers for research, diagnosis and treatment of congenital metabolic disorders. In April 2011, the Center for Rare Diseases, which includes congenital metabolic disorders, was founded at Heidelberg University Hospital in order to further advance research and patient care.Literature:
Dr. Annette Tuffs | idw
How gut bacteria can make us ill
18.01.2017 | Helmholtz-Zentrum für Infektionsforschung
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
18.01.2017 | Life Sciences
18.01.2017 | Health and Medicine
17.01.2017 | Earth Sciences