Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Insights into side effects of thalidomide using magnetic nanoprobes

05.03.2012
Tokyo Tech’s Hiroshi Handa and colleagues have identified a key protein— cereblon —that plays a key role in the development of birth defects associated with thalidomide using unique sub-micrometer functionalized magnetic nanobeads.
The discovery opens up possibilities for the development of alternative and safer drugs for the treatment of multiple myeloma and leprosy.
Hiroshi Hanada describes his research on magnetic particles for biomedicine in a video interview in the latest Feb 2012 issue of Tokyo Tech’s on line newsletter the Tokyo Tech Bulletin: http://www.titech.ac.jp/bulletin/

Details about Hiroshi Handa’s report on the ‘Identification of a Primary Target of Thalidomide Teratogenicity’ published in Science 327, 1345 (2010).

Thalidomide was prescribed as a sedative for pregnant women to treat morning sickness in the late 1950s. It was removed from the market in the early 1960s, when its use was linked to birth defects including shortened or absent limbs, as well as ear, cardiac and gastrointestinal malformations. However, within a few years the powerful pain relief properties of thalidomide for leprosy patients suggested that the drug may yet have medical benefits. In the 1990s it was also proven to be effective in the treatment of the cancer multiple myeloma.

It is still little understood how use of thalidomide leads to the development of birth defects, and tight restrictions are maintained over administration of the drug to treat leprosy and cancer. Insights into the mechanism behind the toxic effects of thalidomide on pregnant women could help to find ways to avoid these side effects and release the potential of the drug as a powerful medical aid.

Researchers at Tokyo Tech have recently reported the development of high-performance affinity beads – magnetic beads 200 nm in diameter that can be attached to drugs and other compounds, allowing one-step affinity purification of drug targets and an insight into how the drugs act [1]. As Hiroshi Handa and his colleagues explain, “Currently, most commercially available drugs and physiologically active substances have been brought to market without knowledge of factors interacting with the drugs and the substances.” Handa have now applied the beads to unravelling the mystery behind the birth defects caused by thalidomide [2].

The researchers used ferrite glycidyl methacrylate beads for purity affiliation of thalidomide, and identified cereblon as a protein that binds directly with the drug. The researchers then performed in vivo experiments in zebrafish, which were recently shown to be affected by thalidomide during embryonic development and have the useful attribute of a transparent embryo so that the progress of development can be conveniently monitored. Knockdown of genes of interest is also easily implemented in zebrafish. Thalidomide treatment was found to noticeably affect the development of the pectoral fins and otic vesicles, which it is suggested, share common molecular pathways with that of developing limbs and ears in tetrapods.

Zebrafish have a gene that is orthologously similar to cereblon in humans. The researchers investigated the development of embryos in which this gene was knocked down and similar defects were observed as for embryos treated with thalidomide. Co-injection of messenger RNA for the cereblon-orthologous gene was found to rescue these defects. The results suggest a potential means to reverse the developmental problems caused by thalidomide treatment.

The researchers then investigated the role of cereblon in chicks, which are well-established model organisms for studying thalidomide-induced birth defects. Experiments on chicks further supported the conclusion that cereblon is a direct target in thalidomide-induced birth defects.

The action of thalidomide is complex and it is associated with a number of other mechanisms that may also cause problems in fetal development, including oxidative stress and antiangiogenic activity. However, as Handa and his colleagues explain, “identification of thalidomide’s direct target may allow rational design of more effective thalidomide derivatives without teratogenic activity”. The work holds promise for a role of thalidomide in medical treatment that is not blighted by the side effects observed in the past.

References:
[1] T. Ito, H. Ando, T. Suzuki, T. Ogura, K. Hotta,Y. Imamura, Y. Yamaguchi & H. Handa. “Identification of a Primary Target of Thalidomide Teratogenicity,” Science 327, 1345 (2010).
[2]S. Sakamoto, Y. Kabe, M. Hatakeyama, Y. Yamaguchi, & H. Handa. “Development and application of high-performance affinity beads: Toward chemical biology and drug discovery,” The Chemical Record 9, 66-85 (2009).

Further information:
Hidekazu Ueda and Yukiko Tokida
Center for Public Information
Tokyo Institute of Technology
2-12-1, Ookayama, Meguro-ku, Tokyo 152-8550, Japan
E-mail: kouhou@jim.titech.ac.jp
URL: http://www.titech.ac.jp/english/
Tel: +81-3-5734-2975
Fax: +81-3-5734-3661
About Tokyo Institute of Technology
As one of Japan’s top universities, Tokyo Institute of Technology seeks to contribute to civilization, peace and prosperity in the world, and aims at developing global human capabilities par excellence through pioneering research and education in science and technology, including industrial and social management. To achieve this mission, we have an eye on educating highly moral students to acquire not only scientific expertise but also expertise in the liberal arts, and a balanced knowledge of the social sciences and humanities, all while researching deeply from basics to practice with academic mastery. Through these activities, we wish to contribute to global sustainability of the natural world and the support of human life.

Website: http://www.titech.ac.jp/english/

Hidekazu Ueda | Tokyo Institute of Technology
Further information:
http://www.titech.ac.jp/english/

More articles from Life Sciences:

nachricht Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | 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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Gold shines through properties of nano biosensors

17.08.2017 | Physics and Astronomy

Greenland ice flow likely to speed up: New data assert glaciers move over sediment, which gets more slippery as it gets wetter

17.08.2017 | Earth Sciences

Mars 2020 mission to use smart methods to seek signs of past life

17.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>