HAIFA — Prof. Karl Skorecki, a Canadian who made aliyah in 1995, has just led a research team to a significant genetic finding in the field of non-diabetic kidney disease.
Karl Skorecki
Skorecki is a researcher at the Technion – Israel Institute of Technology and the Rambam Medical Center in Haifa. His team includes researchers from Hadassah Medical Center in Jerusalem, Tel Aviv University and the National Institute of Health (NIH) in Washington, D.C.
Kidney disease affects some 40 million people in North America, half a million of whom suffer from final or end-stage kidney disease requiring life-sustaining dialysis or transplantation.
“This is a significant finding,” said Skorecki, a 56-year-old Community Hebrew Academy of Toronto (CHAT) graduate who made aliyah with his wife and five children in 1995 after spending a sabbatical at the Weizmann Institute of Science in Rehovot in 1991.
Until recently, it was thought that only certain rare types of kidney disease were genetic in origin. The new finding suggests that genetic factors play an important role, appearing in almost all forms of kidney disease, with one of the highest ever reported genetically-based set of risk markers for a common disease.
In September 2008, scientists at Johns Hopkins University in Baltimore, Md., designated the importance of gene MYH9, on chromosome 22, as an important genetic marker for kidney disease in African-Americans. Skorecki’s team took this research one step further and narrowed it down to one particular even more predictive “risk allele,” or any of the forms in which a gene for a specific trait can occur.
The finding, which was published in the current issue of Human Molecular Genetics, goes a long way to explaining why African-Americans have a four-fold higher rate and Hispanic Americans a two-fold higher rate of end-stage kidney disease than Americans of European ancestry.
Skorecki was, however, careful to explain that simply possessing the risk allele does not mean an individual will get kidney disease. “The risk allele heightens the susceptibility of an individual, and although in this case that is very powerful – increasing susceptibility by three to 10-fold – it is not Mendelian. In other words, if your dad has it, it is not certain that you will definitely get it, too,” he said. “Most people who have the risk allele will not get kidney disease.”
More often than not, those who do get the disease get it as a secondary condition, as the result of a primary factor such as HIV-AIDS, taking certain drugs, or even consuming a high-salt diet.
For example, the finding explains why African-Americans with AIDS frequently get HIVKN, HIV-related kidney nephropathy, while people of European ancestry hardly every get the condition.
Skorecki also said that although the risk allele is most prevalent among African and Hispanic Americans, it could be present in anyone with African ancestry, though the frequency is much higher in west and south Africa that in north and east.
Interestingly, Ethiopians seem to be protected from the risk allele, a fact that may hold the secret that connects the function of the gene with healthy kidneys. Skorecki and his team are currently working with Ethiopian test cases in Israel, in collaboration with researchers in Ethiopia.
In addition to determining susceptibility, the discovery of the risk variant of the gene makes it relatively easy and cheap to screen at-risk populations, a key measure for the prevention of kidney disease. This could especially prove important in regions of the world where dialysis and transplantation are not available and end-stage kidney disease is fatal.
Skorecki’s group will meet with U.S. public health officials in April at the NIH to determine who to screen, what the implications are for transplantation, and other immediate public health questions. “It’s the fastest I have ever seen a finding turn into public health policy,” Skorecki said. “It’s very gratifying to see that the work one does gets an immediate response in terms of public health.”
In addition to dealing with public heath questions and studying the Ethiopian case, Skorecki and his team are continuing to bring the research to the next plateau. Although they have discovered the risk allele and know how to detect its presence, no group has yet succeeded to find the “causative mutation,” the way in which this allele distorts the function of the kidney’s filtering cells. “That’s the holy grail that everyone is competing for,” he says.
Skorecki and his team are taking several paths to get there: studying the evolutionary history of the risk allele and conducting experimentation on the molecular level.
The hope is that this work will ultimately lead to the development of a drug or recognition of an existing drug that might serve as a preventative or therapeutic solution for kidney disease. “The finding has shed light on the basic physiology of the kidney, and this is a necessary precursor for the design of potential treatment,” Skorecki said.
He has worked on many medical research projects since he arrived in Israel 15 years ago, not all of them related to kidney disease and genetics. He has also participated in cancer and stem cell research.
“I am extremely impressed with the high level of research taking place in Israel. The country has so many other problems and lacks the economic infrastructure of countries like Canada, the U.S., and the countries of Europe, yet the productivity of our research in Israel has certainly been as good or better than [the research I did] before we moved to Israel,” Skorecki said.
“Research does depend on money and equipment. But more so, it depends on human interactions with excellent students and very strong colleagues and there is no shortage of that in Israel.”
He also said that the country has a fluid scientific culture that encourages the free exchange of ideas; special study populations, including Druze and Ashkenazi Jews (though that’s not relevant to his current research), and ahead-of-the-curve legislation on stem cell research.
Even before he became a scientist, he had a great appreciation for the country. “I have always loved Israel – since CHAT,” Skorecki said.
