Encouraging Early Data Suggests Bacterial Replacement May Stall Or Prevent Diseases Linked To Excess Oxalate
GAINESVILLE, Fla. — A beneficial naturally occurring bacterium may provide a safe and effective treatment for children with a rare life-threatening disease that causes recurrent kidney stones and eventually destroys both the kidneys and liver, researchers reported today (11/21).
The outcome of a first-time clinical trial in Cologne, Germany, reveals that nine children with the inherited disease primary hyperoxaluria, characterized by a build-up of calcium and oxalate – responded well to a daily supplement containing a bacterium called Oxalobacter formigenes. The “friendly” bacterium appears to break down calcium oxalate before it can form crystals that are deposited in the kidneys and other organs. The treatment is based on discoveries by University of Florida researcher Ammon Peck regarding the bacterium.
Dr. Bernd Hoppe, director of pediatric nephrology at University Children’s Hospital in Cologne, announced the findings this morning at a scientific meeting in Annapolis, Md., sponsored by the National Institutes of Health and the Oxalosis and Hyperoxaluria Foundation. He said all study participant experienced significant reductions in oxalate levels after four weeks of daily treatment.
Oxalate is found in foods such as peanuts, chocolates, spinach and strongly brewed tea. Why many people lack enough of the bacterium is unclear, although scientists have found that repeated use of antibiotics can, in some individuals, destroy the organism.
“The results of this first small-scale human testing were encouraging beyond my expectations,” Hoppe said. “We found that the treatment brought about significant reduction of oxalate levels in two groups of children – seven of whom still have functioning kidneys and two who are in the end stage of kidney failure. Our findings indicate a definite correlation between the amount of bacteria in the intestines and decreased oxalate excretion in the urine.”
Each child in the study group received two teaspoonfuls per day of the supplement in a paste containing a live specimen of the selected bacterium. The preparation was kept deep-frozen, then quickly thawed at the time of use. Most of the patients did not like the taste of the supplement, which researchers said is similar to unflavored oatmeal.
“The data from this study are so encouraging that we’re now planning to conduct a second study in December in two or three adults and about eight children,” he said. “This time we will assess the effectiveness of the same bacterium given in a capsule instead of the paste. We think the capsules will be easier for patients to accept.”
Primary hyperoxaluria, which represents the extreme end of a spectrum of diseases caused by high oxalate levels, affects only about 1,000 children in the United States and Europe. Children with the disease lose normal kidney function within a few years, and the only effective treatment involves a combined kidney and liver transplant.
Researchers involved in the latest research said the bacterial treatment could potentially benefit millions of people affected by kidney stones. Close to 10 percent of Americans develop kidney stones at some point in their lives.
Hoppe reported that in the eight children with functioning kidneys, oxalate levels went down between 20 percent and 50 percent. He said their oxalate levels remained reduced between 16 percent and 25 percent for two weeks after the treatment was stopped but then gradually increased to pre-treatment levels.
Hoppe credits the treatment with prolonging the lives of the two children who remain on renal dialysis while awaiting kidney transplantation. In these children, he said, significant reductions in blood levels of oxalate were documented during the four-week treatment period, but after treatment ended, oxalate levels gradually returned to their previous levels. He said no obvious changes in overall health were observed during the treatment period.
Peck, who attended the meeting, said, “The data indicate that what was predicted from our extensive studies in animals is reproduced in people. If we continue to see this strong correlation between bacterial replacement and reduced oxalate levels, we may eventually be able to achieve a positive effect in using O. formigenes treatment to prevent kidney stones. Dr. Hoppe has found some proof of concept in these children with life-threatening oxalate disease. Their response indicates that by giving the bacterial supplement, we can initiate the elimination of oxalate before calcium-oxalate crystals begin to form.”
Peck cautioned, “This experimental product is still being developed and refined, and extensive additional clinical studies will be necessary before we can assess its true potential for use in patient care.” Peck is a professor of pathology and laboratory medicine at UF’s College of Medicine.
Through more than a dozen years of studying O. formigene’s role in kidney stone prevention, Peck discovered that the bacterium, when given to rats with hyperoxaluria, prevents the formation of crystals that turn into kidney stones. In the late 1980s and early 1990s, his team cloned the two genes that produce enzymes in this bacteria, capable of degrading oxalic acid into byproducts that can be eliminated in the urine.
Results of Peck’s research led to the creation of Ixion Biotechnology Inc., a private company located at Progress Corporate Park near Alachua, Fla., that provided the supplement for the German trial and is developing other products stemming from Peck’s discoveries.
Peck, an officer in Ixion, holds six U.S. patents on the enzymes that break down oxalate and has licensed the rights to Ixion to develop products based on the discoveries.