Researchers develop new tool for leptin study
means for controlling and better understanding of the function of
this protein, including its role in unwanted cell growth - has been
developed by researchers at the Hebrew University of Jerusalem,
Israel.
For nearly a decade, it has been known that leptin plays an important fat-burning role in humans, leading to considerable excitement about its potential as a treatment for obesity.
But the map of leptin's path through the body - the key to understanding how and why the hormone works - is still incomplete, and the pharmaceutical industry has been unable to target the pathway effectively to develop a therapeutic. Adding to its complexsity, leptin can also have negative consequences, such as, enhancing the spread of tumours.
Now, Arieh Gertler, Professor of Agricultural Biochemistry at Hebrew University, has developed with his team a technique for genetically engineering mutations of the leptin protein.
In experimental work carried out cooperatively with researchers in France, the scientists have developed a model showing which amino acids in leptin are responsible for activating leptin receptors in living cells. By replacing these amino acids with others, they were able to create a leptin variant that could bind with cell receptors, but would be unable to activate them, thereby providing a unique, novel research tool.
The mutated leptin acts as an antagonist competing with the normal leptin in binding to the cell receptors, effectively neuralising the effect of the hormone.
Since leptin is involved in several cell functions, the development of this leptin antagonist could have significant consequences not only for better understanding of leptin action in animals but also on halting undesirable leptin effects in humans, such as undesired cell proliferation in cancer, or in controlling other pathological phenomena in which leptin is a factor, according to the researchers.
Thus far, the researchers have succeeded in creating antagonists of human, sheep, rat and mouse leptins. A company, Protein Laboratories Rehovot, was formed by Prof Gertler and the Hebrew University's Yissum Research Development Co 18 months ago to commercialise the technology.
Further development is currently being pursued towards testing whether leptin antagonists are capable of anticancer activity.
