by Maggie Zhang
Graduate student in the Committee on Microbiology
About one1 in 10 people will develop a kidney stone during their lifetime. The risk is even higher for those suffering from high blood pressure, diabetes, and obesity. And the incidence of forming kidney stones—a process known as nephrolithiasis—is on the rise: from 3.8 percent to 8.8 percent over the last four decades.
The problem is not new. Kidney stones were found in an Egyptian mummy dating back to 4800 BC. Indian texts from around 600 BC recommend a vegetarian diet and urethral syringe of medicated milk, clarified butter, and alkalis. If these failed, surgery was the final treatment.
In a broad sense, our approach to treating kidney stones has remained unchanged over two thousand years later. Even now, patients who develop stones will be advised lifestyle interventions, such as drinking more water and changing to a special diet.
But these changes are often unsustainable and sometimes simply insufficient. Patients who develop one stone have a 50 percent chance of forming another within five to seven years, as well as increased risk of chronic kidney disease, which can eventually lead to kidney failure and the need for dialysis or transplantation. Although advances now allow for less painful and invasive surgeries to remove kidney stones, we’re still not much better at preventing them in the first place.
The source of these painful deposits is oxalate, a chemical naturally present in the human body and found in many foods, such as spinach, beets, and nuts. Though it is normally eliminated as waste through the kidneys, when too much oxalate enters the urine, it can combine with calcium to form the stones.
Research from Hassan’s group has shown that factors secreted by the intestinal bacterium Oxalobacter formigenes can provide a natural solution. The bacteria consume the oxalate in the large intestine and thus reduce what is passed on to the kidneys, reducing the risk of stone formation. Introducing live bacteria directly into the intestines and maintaining them there, however, remains problematic. The team at Oxalo Therapeutics is working on proteins and peptides generated by Oxalobacter that can help transport oxalate from blood into the large intestine and thus reduce the amount entering the urine.
Last December Oxalo presented their ideas at the University of Chicago Innovation Fund finals, managed by the Polsky Center for Entrepreneurship and Innovation. The team—Hassan and Chicago Booth student Yang Zheng—won $250,000 in venture funding to develop a first-in-class therapeutic to treat kidney stones. The Innovation Fund provides critical early capital to push groundbreaking ideas out of the lab and into solutions that can improve the lives of many.
Hassan’s group had already shown that substances derived from Oxalobacter could stimulate oxalate transport by human intestinal cells grown in culture. They had also demonstrated that these substances could decrease urinary oxalate levels in mice with high levels. Thanks to Innovation Fund support, Oxalo Therapeutics will now develop promising Oxalobacter-derived proteins and peptides aimed at reducing oxalate levels in human urine.
The hope is that a daily oral pill made from optimized versions of these proteins and/or peptides will eliminate the problems involved in administering live bacteria. This preventive drug offers significant advantages over treatments, not the least of which is a much more natural method of helping people stay free of kidney stones.
Long before ancient Indians first described their remedies, trillions of bacteria lived in harmony with the human body, providing countless indispensable functions to support human health. Our co-existence with them predates medicine by over two million years. For millennia, the microbes inside us have been experimenting with the best ways to survive, which depends on keeping their homes—us—healthy as well.
Greater understanding of our internal microbial community can help us treat and more importantly prevent disease. Part of the job of the Duchossois Family Institute is to get the right microbes and their products into the people who need them.
Oxalo Therapeutics is on their way to doing just that.
Photo (cropped) by Jakupica/Wikimedia Commons