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UW Medicine researchers exploring kidney regeneration using nanobodies

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UW Medicine researchers exploring kidney regeneration using nanobodies

As one of the leading research institutions in the country, the UW is constantly on the lookout for a big scientific breakthrough. The next major project? Tackling kidney regeneration therapy. The National Institutes of Health has recently sponsored a team of scientists from UW Medicine, Cleveland Clinic, and Lumen Bioscience — a biotechnology company based in Seattle — to tackle human kidney regeneration. 

Kidney regeneration has serious potential to help those currently living with kidney disease. One aspect of kidney disease is the deterioration of the kidney’s filter, the glomerulus; this inhibits the organ’s ability to keep essential proteins and nutrients inside the body and ultimately causes severe damage to the kidneys themselves. By regenerating this filter, scientists are hoping to make deteriorating kidneys function efficiently for longer. 

The team working on this project is a part of the larger (Re)Building A Kidney Consortium that has brought together scientists from universities and clinics around the country to research kidney regeneration. What makes this specific project unique is the novel approach of using nanobodies — small antibodies that have the ability to recognize and bind to other molecules with a high specificity — to deliver a therapy to the kidneys to aid in regeneration. 

Dr. Benjamin Freedman is one of the scientists in the division of nephrology at UW Medicine working on this project.

“What we’re developing is a way to get these nanobodies so that we can inject them into the bloodstream and they would home to the kidneys,” Freedman said. “And we can attach to this nanobody a drug that would then deliver the treatment for regeneration.”

One of the first steps in this process is finding the right nanobody to transport the treatment to the kidneys. Freedman describes the process of searching for the perfect nanobody as a fishing experiment. 

“We use the [kidney] molecule we are interested in and we fish out the one type of nanobody that's going to recognize just that type of molecule,” Freedman said. “We can figure out which one of these nanobodies we’ve caught and make more of them.”

Although Freedman concedes that finding the perfect nanobody is critical to the success of the entire experiment (and consequently one of the riskiest components), the experiment is still far from over once the nanobody is determined. Figuring out the drug that is going to give the most desirable results in pairing with the chosen nanobody is no small feat.

Each partner will tackle a different aspect of the research. The team at Lumen Bioscience, led by Jim Roberts, will figure out the nanobody that will bring the determined drug to the kidney cells safely and at a high concentration. Freedman’s specific role is to grow primitive forms of kidneys and develop techniques to stimulate regeneration in them. The team at the Cleveland Clinic, led by Oliver Wessely, has the responsibility of determining what drugs are most likely to stimulate regeneration of the kidney cells. Finally, Stuart Shankland, another nephrologist with UW Medicine, will practice the developed therapy in mice to ensure it works properly and effectively.

The big task ahead is figuring out how to reach the ultimate goal of creating the ideal therapy. The project timeline is five years and the major steps involve setting up the tools for success, determining the strategy to move forward based on experiments, and testing the therapy to prove it works and to figure out just what it is capable of. 

While much of the major research has yet to begin, and how the eventual treatment will look is still up in the air, the ultimate goal is to find a medically relevant solution that can improve the lives of those living with kidney disease.

“One in every 10 people worldwide has some level of kidney disease, and right now we don't have a lot of drugs that really help people with these problems,” Freedman said. “If we could just get these filters to last just a little bit longer a lot of these patients would actually never need a kidney transplant.”

Through the (Re)Building A Kidney website, patients and the general public, whom this research is being performed for, can have immediate access to the data of this project as it becomes available. There is a lot of work ahead, but this project presents hope for those living with kidney disease through the exploration of the potential these tiny — yet powerful — nanobodies hold.

Reach reporter Katie Wilton at news@dailyuw.com. Twitter: @katiegwilton

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