Navigation Links
Deadly genetic disease prevented before birth in zebrafish
Date:3/20/2008

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.

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."


'/>"/>

Contact: Beth Miller
millerbe@msnotes.wustl.edu
314-286-0119
Washington University School of Medicine
Source:Eurekalert

Related biology news :

1. Scripps research team blocks bacterial communication system to prevent deadly staph infections
2. Northwestern to expose most deadly infectious diseases in 3-D
3. Best treatment identified to reduce deadly Staph infections
4. Research unveils new hope for deadly childhood disease
5. Does the desire to consume alcohol and tobacco come from our genetic makeup?
6. Diverse genetic abnormalities lead to NF-κB activation in multiple myeloma
7. Many parents at-risk for cancer disclose genetic test results to children
8. Genetics determine optimal drug dose of common anticoagulant
9. Claims of sex-related differences in genetic association studies often not properly validated
10. American College of Medical Genetics responds to new FDA labeling decision for warfarin
11. UNC study questions FDA genetic-screening guidelines for cancer drug
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/20/2017)... ALLENTOWN, Pa. , March 20, 2017 ... PD 2.0 personal spirometer and Wellness Management System (WMS), ... Founded in 2010, PMD Healthcare is a ... Company with a mission dedicated to creating innovative solutions ... of life. With that intent focus, PMD developed the ...
(Date:3/13/2017)... Future of security: Biometric Face Matching software  ... ... Matching enables to match face pictures against each other or against large databases. ... Systems) ... the fastest software for biometric Face Matching on the market. The speed is ...
(Date:3/9/2017)... VIEW, Calif. , March 9, 2017 ... 23andMe , the leading personal genetics company, are using ... now provide customers with personalized nutrition plans that consider ... but also genetic markers impacting how their body may ... food decision support platform uses biometrics such as Body ...
Breaking Biology News(10 mins):
(Date:5/16/2017)... Telehealth has long been a standalone ... has been kept completely separate from discussions about ...   Logicalis Healthcare Solutions , the healthcare-focused arm ... managed services provider ( www.us.logicalis.com ), there is ... between telehealth, imaging, and EHR optimization that healthcare ...
(Date:5/16/2017)... ... ... On Tuesday, May 23 at 10:30 AM, James Sherley, Director of Asymmetrex ... that his company has recently achieved in collaboration with its partner, AlphaSTAR Corporation ... first partnering conference, Cell & Gene Exchange 2017 . In addition to ...
(Date:5/15/2017)... ... 15, 2017 , ... Catalent Pharma Solutions, the leading global ... health products, today announced that it has signed an agreement with Therachon AG, ... clinical development of TA-46, a novel protein addressing achondroplasia, which is the most ...
(Date:5/15/2017)... ... May 15, 2017 , ... Continuing to build off ... has today launched its first-ever cross-medium campaign, #StandFirm, with high-visibility social and digital ... social media channels, emphasizing Algenist’s stance on individuality and disruption: , We ...
Breaking Biology Technology: