Polycystic kidney disease (PKD) develops away from the prying eyes of researchers who are trying to better understand this devastating condition that affects over 12 million people.
That's why Benjamin Freedman, PhD, an Instructor in Medicine at Brigham and Women's Hospital and Harvard Medical School, is working to take PKD out of the patient.
"If we can regenerate PKD kidney cells in a dish, then we can observe how PKD and cysts develop," said Dr. Freedman. "This process will allow us to determine the cellular basis for PKD complications and determine whether they can be alleviated therapeutically."
Dr. Freedman's research, funded in part by a Young Investigator's Grant from the National Kidney Foundation, focuses on genome modification techniques applied to human induced pluripotent stem cell lines derived from patients with PKD. Differentiating these cells into kidney tissue will allow the creation of models to understand PKD pathophysiology. Eventually, these PKD kidney cells will serve as testing ground to assess safe medication doses for human cells and tissues before taking new treatments to clinical trial.
Dr. Freedman, 35, became interested in stem cells and regeneration while studying biochemistry at the University of Pennsylvania. He began applying his knowledge to kidney disease because both his grandfather and uncle were on dialysis. That interest took him to the laboratory of Dr. Joseph Bonventre in Boston, where he trained as a fellow from 2010-2013 and began his current research.
Initial papers on the process of generating PKD cells have already been published, and Dr. Freedman believes that drug screens for PKD could start within the next five years.
"We will first see the use of these kidney-in-a-dish models as a way of analyzing toxicology," he said. "The biopharmaceutical companies are going to be very interested in looking into these stem-cell derived tissues for researching new therapies."
Dr. Freedman's research is also forming the background for a larger project – regenerating kidney cells from PKD patients, editing those cells to remove the PKD mutation, and putting these disease-free cells back into patients. This process essentially creates immunocompatible kidneys that could be designed on demand, without the risk of rejection.
"From a broader level, whatever we learn about making kidney tissue will also be relevant to the kidney patient population as a whole," Dr. Freedman said. "If we learn to do this properly, and it's safe and compatible, we'll find new ways to create kidneys for all patients with kidney failure."
Dr. Freedman believes his work hinges upon continued collaboration and support from patients, researchers and foundations alike.
"I'm very thankful to the National Kidney Foundation for supporting this research," said Dr. Freedman. "They gave me my first independent grant as a faculty member. It's a tough time for researchers and it's important that we communicate with the public and get the word out. These are hard problems to solve. They aren't going to be solved over night or by a single individual. They will be solved by a community coming together to figure out the best approach to tackling a problem."