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 . 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 .
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.
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:
Hidekazu Ueda | Tokyo Institute of Technology
Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)
CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
19.01.2017 | Earth Sciences
19.01.2017 | Life Sciences
19.01.2017 | Physics and Astronomy