Navigation Links
Researchers discover hereditary enzyme deficiency

An international research team headed by Professor Dr. Thomas Dierks at Bielefeld University has discovered a hereditary enzyme deficiency. It is a subform of the mucopolysaccharidosis syndrome and has been termed MPS IIIE or after its discoverer 'Dierks's disorder'. It leads to a progressive loss of mental abilities in mice, particularly to learning and coordination difficulties along with forgetfulness. The biochemist Dierks and his team have not only identified the disorder but also developed a treatment concept. Their findings are being published this week (CW 24) in the renowned journal 'Proceedings of the National Academy of Sciences of the USA' (PNAS).

Enzymes control the constitution and degradation of nutrient and messenger substances in the human body. If the body produces a defective enzyme due to an inherited deficiency, this control breaks down. The individual becomes ill because, for example, substances can no longer be degraded and accumulate in the body.

Dierks and his colleagues have discovered that a deficiency of the enzyme arylsulfatase G (ARSG) triggers the disease MPS IIIE in mice. Actually, the enzyme among others - is responsible for degrading the carbohydrate heparan sulfate. This process occurs within the cells inside the lysosomes. These 'recycling plants' in the cells break down no longer needed heparan sulfate molecules into their smallest components, which later are used to reassemble new molecules.

Heparan sulfate is a long-chain molecule. This chain can only be broken down from one end and only step by step. This process is performed by various enzymes including ARSG. If one of the enzymes is deficient because of a genetic defect, the complete degradation process comes to a stop. The molecular chains remain largely intact and accumulate more and more in the lysosome, which finally stops functioning. Then, also other substances such as proteins and lipids also accumulate because they are no longer degraded. The lysosome grows and grows until it damages the entire cell and eventually destroys it.

At the beginning of the study (2003), only seven of the enzymes involved in the degradation of heparan sulfate were known. Dierks and his team were searching specifically for one missing enzyme. They knew that a total of at least nine different enzymes would be needed for the complete degradation of heparan sulfate two of these (both of them sulfatases) had still not been discovered. Every inherited deficiency in one of these enzymes corresponds to a disorder belonging to the mucopolysaccharidosis syndrome. 'When we started the study, we suspected that arylsulfatase G was involved in the degradation of heparan sulfate', says Dierks. To test this assumption, his team bred mice in which arylsulfatase G was deficient. Their suspicion was confirmed: With increasing age, the mice revealed high concentrations of heparan sulfate in the brain, the liver, and the kidneys. Professor Jeffrey D. Esko from the University of California San Diego (USA) is also working in this project. He and his team analysed tissue samples with a mass spectrometer and confirmed the finding that the blocked cleavage of a specific sulfate group is the cause of the accumulation of heparan sulfate.

Using behaviour tests, Dierks's team found that mice with an ARSG deficiency suffer from cognitive problems once they reach the age of 12 months. If they enter an open field, they stick to the safer periphery and, unlike healthy littermates, do not have the courage to explore the centre. They also fail to master a water maze. For a long time, the mice had been trained successfully to swim through a pool filled with a milky liquid until they found a platform hidden beneath its surface. However, as soon as they were 12 months old, the mice failed to memorize where the platform was located. They took much longer than before to discover it. Younger and healthy mice had no problems in finding the platform again. The defect is in the brain. In a study of tissue samples from the animals' cerebellum, the research team showed that through the accumulation of heparan sulfate, the Purkinje cells in the cerebellum die off and accompanied by inflammation are replaced by new cells. However, according to Dierks, these glia cells have only a supporting function and do not form any new connections to nerve cells.

A major success for the researchers is that their findings can be used to develop a treatment for this hereditary disorder and test this treatment on ARSG deficient mice. They are producing ARSG enzyme in a biotechnology process with the help of genetically modified cell cultures. In sick mice that are regularly injected with a solution containing the enzyme, further damage to their organs should be stopped, Dierks believes. Similar treatments are successfully applied to patients with other mucopolysaccharidosis disorders. 'The biochemical processes underlying such lysosomal storage disorders are principally the same in all mammals. However, effects are more severe in human beings because of their greater life span', says Dierks. An early diagnosis of these disorders can be difficult because the onset is frequently insidious. Sometimes, the disorder can only be recognized through its symptoms in adolescence. And then the diagnosis is difficult for a physician, Thomas Dierks says, 'because systematic screenings are performed only in childhood, and one does not initially consider a genetic cause. However, treatment has to start as early as possible'. 'Dierks's disorder' can be diagnosed unequivocally with a mass spectrometer the researchers have developed their own procedure for this.


Contact: Prof. Dr. Thomas Dierks
University of Bielefeld

Related biology technology :

1. New England Biolabs Introduces Polbase, an Information Repository of Scientific Data for Polymerase Researchers
2. In new quantum-dot LED design, researchers turn troublesome molecules to their advantage
3. Multidisciplinary team of researchers develop world’s lightest material
4. Researchers shrink tumors and minimize side effects using tumor-homing peptide to deliver treatment
5. Innovative MetaMorph® NX Software Shatters Barriers Between Researchers and Image Analysis Goals with Exclusive Visual Workflow
6. UCLA researchers demonstrate fully printed carbon nanotube transistor circuits for displays
7. Penn and Brown researchers demonstrate earthquake friction effect at the nanoscale
8. Two Top Biological Imaging Centers Offer Powerful Free Online Tool to Researchers, Educators, and Public
9. Researchers develop one of the worlds smallest electronic circuits
10. MU researchers identify key plant immune response in fight against bacteria
11. Researchers realize high-power, narrowband terahertz source at room temperature
Post Your Comments:
Related Image:
Researchers discover hereditary enzyme deficiency
(Date:11/25/2015)... , Nov. 25, 2015  Neurocrine Biosciences, Inc. ... Gorman , President and CEO of Neurocrine Biosciences, will ... Conference in New York . ... visit the website approximately 5 minutes prior to the ... replay of the presentation will be available on the ...
(Date:11/25/2015)... ... November 25, 2015 , ... A long-standing ... Aerospace Professionals (OPBAP) has been formalized with the signing of a Memorandum of ... with OPBAP leaders Capt. Karl Minter and Capt. Albert Glenn Tuesday, November 24, ...
(Date:11/25/2015)... , November 25, 2015 ... Research Report is a professional and in-depth study ...      (Logo: ) , ... of the industry including definitions, classifications, applications and ... provided for the international markets including development trends, ...
(Date:11/24/2015)... 2015  Asia-Pacific (APAC) holds the third-largest share ... The trend of outsourcing to low-cost locations is ... volume share for the region in the short ... in the CRO industry will improve. ... ), finds that the market earned revenues ...
Breaking Biology Technology:
(Date:11/26/2015)... 2015 Research and Markets ( ) ... Sensors - Technology and Patent Infringement Risk Analysis" ... --> Fingerprint sensors using capacitive technology ... fingerprint sensor vendor Idex forecasts an increase of 360% ... devices and of the fingerprint sensor market between 2014 ...
(Date:11/20/2015)... Connecticut , November 20, 2015 ... authentication company focused on the growing mobile commerce market ... CEO, Gino Pereira , was recently interviewed on ... interview will air on this weekend on Bloomberg ... Latin America . --> NXTD ) ("NXT-ID" ...
(Date:11/19/2015)... , Nov. 19, 2015  Based on its in-depth ... Sullivan recognizes BIO-key with the 2015 Global Frost & ... Frost & Sullivan presents this award to the company ... to the needs of the market it serves. The ... meets and expands on customer base demands, the overall ...
Breaking Biology News(10 mins):