Study Offers Hope of Kidney Disease Treatment : Medicine: UCLA researchers find that the anti-cancer drug taxol halts the growth of destructive cysts in mice.
UCLA researchers report that they have opened the door to what may be the first effective treatment for a devastating inherited kidney disease that affects more than 500,000 Americans.
Working with mice with a naturally occurring form of the disease, called polycystic kidney disease, the researchers have shown that the anti-cancer drug taxol can halt the growth of the cysts that cause the destruction characteristic of the disease. Compared to untreated mice with the disorder that died four to five weeks after birth, those that received the drug lived several months before they were sacrificed for study, according to the report, which appears today in the British journal Nature.
“This is the first time that a medication has been given to an animal with polycystic kidney disease that stopped the disease in its tracks,” said Dr. Jared Grantham, a nephrologist at the University of Kansas Medical Center and chairman of the Polycystic Kidney Research Foundation. “That’s a very significant achievement, and I’m personally pretty excited about it.”
Physicians at UCLA hope to begin a multicenter clinical trial of the drug in humans within a year, according to UCLA molecular geneticist David Woo, head of the team that did the research. The path toward such a trial is a little smoother than usual, he added, because taxol is already approved for treatment of ovarian, breast and lung cancers.
Dr. William Bennett, a nephrologist at the Oregon Health Sciences University and chairman of the Polycystic Council of the National Kidney Foundation, cautioned that there are differences between the human and the mouse forms of the disease. Nonetheless, he said, “It is very encouraging that there is something that will do this (stop the disease).” Even if taxol proves not to be the best drug for humans, he said, “this will give us a lot of clues to help us find others.”
Polycystic kidney disease occurs in approximately one out of every 800 people. Victims are born with thousands of microscopic cysts in their kidneys. These cysts accumulate fluid and grow in size over three to five decades, eventually destroying the kidney. In the last stages, patients require kidney dialysis to clean waste products from their blood and kidney transplants, at a yearly cost to Medicare of more than $750 million.
There is no known treatment that can halt progression of the disease. Most therapy is of a supportive nature that limits infections and includes dietary restrictions that minimize the accumulation of noxious byproducts.
The mouse model used by Woo is actually like a more severe form of the disorder, called infantile recessive polycystic kidney disease. This form strikes only about one in 16,000 people, but is much more devastating because it progresses extremely rapidly, usually causing death before the age of 20.
But, Woo said, “there is no reason to believe that the pathogenesis of the slower form of the disease is any different from the more severe form,” a view that is echoed by Grantham and Bennett.
German scientists have recently developed a rat model of the more common form of the disease. Woo did not work with it originally because studies with rats are substantially more expensive than those with mice, but he is planning new studies to determine whether taxol will work in this model as well.
Taxol was originally isolated from the bark of the Pacific yew tree and was initially in short supply because of the difficulties of obtaining enough bark to process. But drug companies have successfully devised techniques to isolate it from needles and branches of related shrubs, and currently there is no shortage of the drug.
