Gene therapy method developed to target damaged kidney cells

July 5, 2018, Washington University in St. Louis
In this slide, bright green depicts genetic material delivered by a synthetic virus to mouse kidney cells, while the red stain shows cells that cause chronic kidney disease. New research led by Washington University School of Medicine in St. Louis has shown, in mice, that genetic material can be delivered to damaged cells in the kidneys, a step toward developing gene therapy to treat chronic kidney disease. Credit: YOICHIRO IKEDA/Washington University

Gene therapy has gained momentum in the past year, following the federal government's approval of the first such treatments for inherited retinal diseases and hard-to-treat leukemia. Now, research led by Washington University School of Medicine in St. Louis has shown, in mice, that genetic material can be delivered to damaged cells in the kidneys, a key step toward developing gene therapy to treat chronic kidney disease.

The potentially fatal condition affects 30 million Americans, most of whom don't realize they have chronic kidney disease. No cure exists, and current treatments for end-stage disease mostly are limited to dialysis and kidney transplant. However, the researchers said gene therapy could provide a way to deliver that slow or reverse cell damage that leads to chronic kidney disease.

The findings are published July 5 in the Journal of the American Society of Nephrology.

"Chronic kidney disease is an enormous and growing problem," said senior author Benjamin D. Humphreys, MD, Ph.D., director of the Division of Nephrology at Washington University. "Unfortunately, over the years, we haven't developed more effective drugs for the condition, and this reality is leading us to explore gene therapy."

Diabetes, hypertension and other conditions cause chronic kidney disease, which occurs when damaged kidneys cannot effectively filter waste and excess fluids from the body. Because symptoms such as nausea, vomiting, sleep disturbances and swollen limbs are common and nonspecific to the disease, most people don't realize they have chronic kidney disease until irreparable organ damage occurs. Advanced chronic kidney disease also leads to cardiovascular disease, and patients with kidney failure have much higher rates of death from cardiovascular causes than those with healthy kidneys.

"Part of the reason there have been so few advances in kidney disease treatment is because the kidney is complex, and we don't fully understand the disease process," said Humphreys, the Joseph Friedman Professor of Renal Diseases in Medicine. "However, scientists are making progress, and I am optimistic."

Credit: CC0 Public Domain

To that end, Humphreys and his team—including researchers from Harvard University and Massachusetts Institute of Technology—focused on whether adeno-associated virus (AAV), a relative of the virus that causes the common cold, could deliver genetic material to targeted kidney cells. Until now, no such virus has been capable of delivering genetic material to the kidney, and the new research provides a proof of concept for this approach.

The researchers evaluated six AAV viruses, both natural and synthetic, in mice and in stem-cell-derived human kidney organoids. A synthetic virus, Anc80, created by one of the researchers proved successful in reaching two types of cells that contribute to ; these cells secrete proteins that gum up the organ and cause irreversible damage. The researchers also showed that the genetic material carried by Anc80 was transferred successfully to the targeted kidney cells. That same virus also was used by the researchers in gene therapy strategies to treat mice with kidney scarring.

"This was a happy surprise," Humphreys said. "We were not expecting this."

However, Humphreys cautioned that researchers are still early in the process. In future research, scientists will encounter several challenges, such as the need to identify a gene that can extensively correct damaged kidney , he explained. Another issue involves refining the boundaries of gene delivery to prevent delivery of the synthetic to other organs.

"The interesting thing about the adeno-associated viruses is that they persist in the body for many months, potentially giving a therapeutic gene a chance to do its work," Humphreys said. "Chronic kidney disease is a slowly progressive so that is an advantage. After many more years of research, we could envision that patients would need injections maybe twice a year as opposed to every week, like with chemo.

"There has been so little innovation in treatment," he said. "We believe this is a positive step forward."

Explore further: Researchers identify potential new targets for treating kidney disease

More information: "Efficient Gene Transfer to Kidney Mesenchymal Cells Using a Synthetic Adeno-Associated Viral Vector," Journal of the American Society of Nephrology (2018). DOI: 10.2215/ASN.2018004026

Related Stories

Researchers identify potential new targets for treating kidney disease

July 23, 2015
Chronic diseases such as diabetes and hypertension cause injury to the kidneys, which can lead to scarring and the development of chronic kidney disease. By identifying proteins important to this scarring process, researchers ...

Australian breakthrough in stem cell kidney research

May 4, 2018
New research led by the Murdoch Children's Research Institute (MCRI), has combined gene editing technology with stem cell kidney regeneration to correct a patient's gene mutation.

Massive single-cell survey of kidney cell types reveals new paths to disease

April 6, 2018
The kidney is a highly complex organ - far beyond a simple filter. Its function requires intricate interactions between many highly specialized cell types to extract waste, balances body fluids, form urine, regulate blood ...

First drug approved for most common inherited kidney disease

April 24, 2018
The U.S. Food and Drug Administration has approved the first drug to slow kidney decline in patients with the most common inherited kidney disease.

1 in 7 Americans has kidney disease: CDC

June 9, 2017
(HealthDay)—Thirty million American adults have chronic kidney disease—but many don't know it.

Researchers move one step closer towards functioning kidney tissue from stem cells

March 2, 2018
Researchers from the Murdoch Children's Research Institute (MCRI), University of Melbourne and Leiden University Medical Centre (LUMC) in The Netherlands have made an important step towards making human kidneys from stem ...

Recommended for you

Researchers a step closer to understanding how deadly bird flu virus takes hold in humans

November 19, 2018
New research has taken a step towards understanding how highly pathogenic influenza viruses such as deadly bird flu infect humans.

Infants born to obese mothers risk developing liver disease, obesity

November 16, 2018
Infant gut microbes altered by their mother's obesity can cause inflammation and other major changes within the baby, increasing the risk of obesity and non-alcoholic fatty liver disease later in life, according to researchers ...

New study shows NKT cell subsets play a large role in the advancement of NAFLD

November 16, 2018
Since 2015 it has been known that the gut microbiota could have a direct impact on nonalcoholic fatty liver disease (NAFLD), which affects up to 12% of adults and is a leading cause of chronic liver disease. In the November ...

Antibiotic prescribing influenced by team dynamics within hospitals

November 15, 2018
Antibiotic prescribing by doctors is influenced by team dynamics and cultures within hospitals.

Discovery suggests new route to fight infection, disease

November 14, 2018
New research reveals how a single protein interferes with the immune system when exposed to the bacterium that causes Legionnaires' disease, findings that could have broad implications for development of medicines to fight ...

New research aims to help improve uptake of hepatitis C testing

November 14, 2018
New research published in Scientific Reports shows persisting fears about HIV infection may impact testing uptake for the hepatitis C Virus (HCV).

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.