Transplant Drug May Treat Deadly Kidney Disease
An anti-rejection drug widely used in organ transplants could provide the first useful treatment for polycystic kidney disease, a deadly disorder caused by a single defective gene.
Studies in mice show that the drug, rapamycin, can reverse the normally unstoppable growth of kidneys associated with the disease. Studies of a small number of humans suggest that it could work in them as well, the team reported Monday in the Proceedings of the National Academy of Sciences.
For the record:
12:00 a.m. March 25, 2006 For The Record
Los Angeles Times Saturday March 25, 2006 Home Edition Main News Part A Page 2 National Desk 1 inches; 51 words Type of Material: Correction
Kidney disease -- An article in Tuesday’s Section A said that in the most common form of polycystic kidney disease, if one parent has the defective gene, each child will develop the disease. In fact, if one parent has the gene, a child has a 50% chance of developing the disease.
Because the drug is already approved by the Food and Drug Administration and known to be safe, clinical trials in patients with the disease could begin rapidly, said professor Thomas Weimbs of UC Santa Barbara, who led the study.
About 600,000 Americans and 12.5 million people worldwide have the disease, which generally causes kidney failure requiring either a lifetime of dialysis or a kidney transplant. There is no treatment for the disorder.
“It looks like this drug has great potential to stop the expansion of cysts [in the kidneys] and thus prevent kidney failure,” said Dan Larson, president and chief executive of the PKD Foundation in Kansas City, Mo. “It’s a very promising development.”
The most common form of PKD is a so-called autosomal dominant genetic disease, meaning that if a parent carries the defective gene, each child will inherit it and develop the disease.
Symptoms begin appearing early in adulthood, marked by the growth of cysts in the kidneys and other organs. As the disease progresses, each kidney -- normally the size of a fist -- grows to the size of a football or basketball, reaching a weight of as much as 38 pounds.
As the kidney grows, it loses its ability to filter liquids from the bloodstream and eventually fails.
About 10 years ago, researchers discovered that the disorder is caused by a defect in a gene called polycystin-1.
Weimbs and his colleagues recently demonstrated that the gene regulates a signaling protein called mTOR that controls cell growth and proliferation. Scientists already knew that rapamycin inhibited mTOR, but they were not aware of the protein’s role in cyst growth.
The Santa Barbara team found that giving rapamycin to mice with an experimental form of PKD sharply reduced kidney growth.
They then looked at humans who had received kidney transplants for the disease. Typically, surgeons leave the diseased kidneys in the body, adding the transplant as a third kidney. Rapamycin is often used in the transplant to prevent organ rejection.
The team found four patients who had received rapamycin and had CT scans of their kidneys immediately before or after the transplant and two years later. They observed that the diseased kidneys in the rapamycin recipients had shrunk by about 25% over the two-year period after surgery, while kidneys in those who received other anti-rejection drugs remained the same size.
“We were very excited about it,” Weimbs said. “It shows that the effect goes in the right direction. Nothing else has ever been shown to reverse the growth of kidneys in humans.”
He predicted that clinical trials of the drug could begin in Europe later this year and in the U.S. as early as next year.
