Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Deadly genetic disease prevented before birth in zebrafish

25.03.2008
Finding offers potential for helping humans

By injecting a customized "genetic patch" into early stage fish embryos, researchers at Washington University School of Medicine in St. Louis were able to correct a genetic mutation so the embryos developed normally.

The research could lead to the prevention of up to one-fifth of birth defects in humans caused by genetic mutations, according to the authors.

Erik C. Madsen, first author and an M.D./Ph.D. student in the Medical Scientist Training Program at Washington University School of Medicine, made the groundbreaking discovery using a zebrafish model of Menkes disease, a rare, inherited disorder of copper metabolism caused by a mutation in the human version of the ATP7A gene. Zebrafish are vertebrates that develop similarly to humans, and their transparency allows researchers to observe embryonic development.

... more about:
»Genetic »Madsen »Menkes »Mutation »Treatment »copper »morpholino

Children who have Menkes disease have seizures, extensive neurodegeneration in the gray matter of the brain, abnormal bone development and kinky, colorless hair. Most children with Menkes die before age 10, and treatment with copper is largely ineffective.

The research is published this month in the Proceedings of the National Academy of Sciences' advance online edition.

The development of organs in the fetus is nearly complete at a very early stage. By that time, the mutation causing Menkes disease has already affected brain and nerve development.

Madsen and Bryce Mendelsohn, also an M.D./Ph.D. student at the School of Medicine, wondered if they could prevent the Menkes-like disease in zebrafish by correcting genetic mutations that impair copper metabolism during the brief period in which organs develop. Both students work in the lab of Jonathan D. Gitlin, M.D., the Helene B. Roberson Professor of Pediatrics at the School of Medicine and director of Genetics and Genomic Medicine at St. Louis Children's Hospital.

The researchers used zebrafish with two different mutations in the ATP7A gene, resulting in a disease in the fish that has many of the same characteristics of the human Menkes disease. Madsen designed a specific therapy to correct each mutation with morpholinos, synthetic molecules that modify gene expression. The zebrafish embryos were injected with the customized therapy during the critical window of development, and the researchers found that the zebrafish hatched and grew without any discernable defects.

"This method of copper delivery suggests that the prevention of the neurodegenerative features in Menkes disease in children may be possible with therapeutic interventions that correct the genetic defect within a specific developmental window," Madsen said.

The genetic mutations Madsen and the researchers worked with are caused by splicing defects, or an interruption in genetic code. The morpholinos prevent that interruption by patching over the defect so the gene can generate its normal product.

"Consider the genetic code as a book, and someone has put in random letters or gibberish in the middle of the book," Madsen said. "To be able to read the book, you have to ignore the gibberish. If we can make cells ignore the gibberish, or the splicing defect, the fetus can develop normally."

Up to 20 percent of genetic diseases are caused by splicing defects, Madsen said, so this treatment method could potentially be used for many other genetic diseases.

"The idea is that we can modify the treatment to target a specific mutation and design molecules to alter gene function in the same way the morpholino oligonucleotides can," Gitlin said.

The work is an important step toward personalized medicine, which can tailor treatment to an individual's genetic makeup.

"Eventually we would like to know each person's genome sequence so we know what mutations each person has that may lead to disease," Gitlin said. "That way, you don't get a drug for cancer that works against any kind of cancer, you get a drug for the specific mutation that causes your cancer. That's what personalized medicine is all about."

Beth Miller | EurekAlert!
Further information:
http://www.wustl.edu

Further reports about: Genetic Madsen Menkes Mutation Treatment copper morpholino

More articles from Life Sciences:

nachricht The dense vessel network regulates formation of thrombocytes in the bone marrow
25.07.2017 | Rudolf-Virchow-Zentrum für Experimentelle Biomedizin der Universität Würzburg

nachricht Fungi that evolved to eat wood offer new biomass conversion tool
25.07.2017 | University of Massachusetts at Amherst

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA mission surfs through waves in space to understand space weather

25.07.2017 | Physics and Astronomy

Strength of tectonic plates may explain shape of the Tibetan Plateau, study finds

25.07.2017 | Earth Sciences

The dense vessel network regulates formation of thrombocytes in the bone marrow

25.07.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>