Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New approach offers potential drug-discovery shortcut

19.04.2004


Researchers find drug that may suppress genetic mutation using a novel screening approach

Researchers at Massachusetts General Hospital have developed a way of identifying promising new drugs that may get around a major challenge in drug discovery. In the May issue of Nature Biotechnology the team from the MGH Cardiovascular Research Center (CVRC) describes using an animal model to screen for a compound that suppresses a serious genetic mutation. Their success did not rely on first identifying a molecular target for the new drug, something that is a key bottleneck in current procedures. The study is being released today on the journal’s website.

"Currently most drugs are designed to act on a specific protein, but for most diseases we still don’t know what the protein targets should be," says Randall Peterson, PhD, of the MGH CVRC, the paper’s lead author. "This is a totally different approach that shows how, without knowing the best target, you can screen for drugs that could reverse a disease and in the process learn something new about the underlying biology."



The researchers started with embryos of zebrafish – a tiny tropical fish used as a model of vertebrate development – with a mutation called gridlock, which prevents the correct development of the circulatory system in the lower portion of the body. A panel of these embryos was exposed to a very diverse library of small molecules – 5,000 in all – to see if any would prevent expression of the gridlock mutation. Two similar molecules were identified that suppressed the mutation, allowing the embryos to develop normally. The one that appeared more powerful, called GS4012, was chosen for further study.

The gridlock-suppressing effects of GS4012 were found to vary with dosage, and no vascular abnormalities were seen at the doses studied. Application of the compound appeared to be most effective at a developmental stage right before and during the formation of major vascular structures. Further experiments showed that GS4012 appears to promote the activity of the angiogenesis factor VEGF and also induces the development of vascular networks in cultured human vascular cells.

"We had a strain of fish with a very specific arterial defect, and although we knew which gene was responsible, there was a lot we didn’t know about the molecular processes disrupted by that mutation," says Peterson "We were able to find a compound that could reverse the mutation and are hopeful that it will provide fundamental new insights into vascular development and disease.

"While this molecule may eventually have clinical application in promoting vascular growth after heart attack, stroke or injury, this new way of identifying potential new drugs may have an even greater impact," he adds. In addition to further studying the mechanism behind the action of the gridlock suppressors they identified, the research team hopes to apply this new drug-discovery approach to other diseases.


###
In addition to Peterson, an assistant professor of Medicine at Harvard Medical School, the research team includes senior author Mark Fishman, MD, formerly director of the CVRC and chief of MGH Cardiology, now president of the Novartis Institute for Biomedical Research; Stanley Shaw, MD, PhD, Travis Peterson, David Milan, MD, and Calum MacRae, MB, ChB, of the MGH CVRC; Tao Zhong, PhD, of Vanderbilt School of Medicine; and Stuart Schreiber, PhD, of Howard Hughes Medical Institute at Harvard University. The research was supported by grants from the National Institute of Health, the Ned Sahin Research Fund for Supporting Developmental Plasticity, and a research agreement with Novartis Institute for Biomedical Research.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $400 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women’s Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.

Sue McGreevey | EurekAlert!
Further information:
http://www.mgh.harvard.edu/

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>