Navigation Links
Severe congenital disorder successfully treated in a mouse model for the first time
Date:12/22/2011

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 Krner, 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 Grne 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. Krner 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. Krner. 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," Krner 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.


'/>"/>
Contact: Prof. Dr. rer. nat. Christian Krner
christian.koerner@med.uni-heidelberg.de
49-622-156-39993
University Hospital Heidelberg
Source:Eurekalert  

Related biology news :

1. Severe climate change costs forecast for Pennsylvania, N.C., Tennessee, N.D.
2. Franklin Square to study airway bypass procedure for severe emphysema
3. Severe gestational hypertension may protect against testicular cancer
4. UT Public Health researchers find link to severe Staph infections
5. Preclinical work shows how one gene causes severe mental retardation
6. New center at Georgia Tech aims to improve recovery of soldiers with severe injuries
7. UF makes gene therapy advance in severe genetic disorder
8. Smaller than expected, but severe, dead zone in Gulf of Mexico
9. Research shows rates of severe childhood obesity have tripled
10. Severe breathing disorders during sleep are associated with an increased risk of dying
11. Test could predict which idiopathic pulmonary fibrosis patients will become severely ill
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Severe congenital disorder successfully treated in a mouse model for the first time
(Date:2/8/2017)... Report Highlights The global biosurgery market should ... 2016 at a compound annual growth rate (CAGR) of ... An overview of the global market for biosurgery. - ... and 2016, and projections of compound annual growth rates ... the basis of product type, source, application, and region. ...
(Date:2/7/2017)... WARSAW, Ind. , Feb. 7, 2017 ... global leader in musculoskeletal healthcare, will present at the ... Lotte New York Palace Hotel on Wednesday, February 15, ... A live webcast of the presentation can be accessed ... for replay following the conference via Zimmer Biomet,s Investor ...
(Date:2/6/2017)... 2017 According to Acuity Market Intelligence, ... authorities to continue to embrace biometric and digital ... Automated Border Control (ABC) eGates and 1436 Automated ... than 163 ports of entry across the globe. ... a combined CAGR of 37%. APC Kiosks reached ...
Breaking Biology News(10 mins):
(Date:2/24/2017)... ... 2017 , ... Delpor, Inc. (Delpor), a biotechnology company focused on drug delivery, ... Health (NIMH) for the further advancement of the company’s 3-month olanzapine product ( DLP-119 ... to deliver therapeutic levels of olanzapine for a period of 3 months., “We are ...
(Date:2/24/2017)... , Feb. 24, 2017 Provectus ... or the "Company"), a clinical-stage oncology and dermatology ... the deadline to participate in its previously announced ... consisting of shares of common stock and Series ... holders of listed warrants. As ...
(Date:2/24/2017)... , Feb. 24, 2017 Symic Bio, a ... a new category of therapeutics, announced today the completion ... in peripheral artery disease. The trial will evaluate the ... therapeutic, in the reduction of restenosis following angioplasty. ... development milestone for SB-030," said Nathan Bachtell , ...
(Date:2/24/2017)... Blood Corporation (NYSE: CO ) ("CCBC" or ... laboratory testing, hematopoietic stem cell processing and stem cell ... the third quarter and first nine months of fiscal ... Quarter of Fiscal 2017 Highlights Revenues ... 18.6% to RMB200.9 million ($28.9 million). ...
Breaking Biology Technology: