New Formula, Drug Research Helps Patients Manage PKU
Phenylketonuria (PKU) is a rare genetic disorder in which the body is unable to metabolize phenylalanine, an amino acid found in almost every source of natural protein.
Patients with PKU must follow a strict diet that is low in phenylalanine—and consequently, low in protein—for their whole lives. In order to keep growth on track during childhood, they also must drink a special phenylalanine-free protein formula.
Because the diet is so restrictive—even more so than a vegan diet—patients often don’t comply, especially as they grow into adolescence and adulthood. And because the formula can taste and smell unpleasant, some adult patients even develop an aversion to it.
But diet noncompliance can actually damage the brain, causing mild cognitive problems, mental retardation, spasticity, tremors, and seizures.
BetterMilk™… From Wisconsin
Gregory Rice, MD, an assistant professor in the Division of Genetics and Metabolism, said that the best way to keep PKU patients on diet is to give them as many options as possible.
He and clinical dietician Sandy van Calcar, PhD, RD, are part of a research team led by Denise Ney, PhD, RD, a professor in the Department of Nutritional Sciences, that developed a new phenylalanine-free formula that may be more palatable for patients.
The formula, called BetterMilk™, contains a natural protein called glycomacropeptide, which has only trace amounts of phenylalanine. Interestingly, glycomacropeptide is found in whey, one of the waste products of the cheesemaking process. “It’s a neat Wisconsin story,” Dr. Rice said.
A Phase I clinical trial found that patients tolerated and liked the new formula, and that their phenylalanine levels were well controlled while taking it.
Dr. Rice said that the formula has two added benefits. First, it’s made from a natural protein instead of a synthesized amino acid blend, which some research suggests may improve growth.
Second, the formula is naturally fortified with other large neutral amino acids, which can “outcompete” phenylalanine for uptake into the blood, brain, and gut.
BetterMilk is now on the medical formulary in six states, and last year, the team applied for a Phase II clinical trial to study its longer-term outcomes.
Evaluating New Medications
A better-tolerated formula is just one strategy for managing PKU, Dr. Rice said. Phenylalanine-reducing medication is another, and Dr. Rice is participating in clinical trials to evaluate several new drugs.
Several years ago, he and Adjunct Professor Jon Wolff, MD, were involved in investigations for Kuvan®, the first Food and Drug Administration-approved drug for treating PKU.
According to Dr. Rice, Kuvan has been found to decrease phenylalanine levels in about 30 to 40 percent of patients who take it, which can help loosen diet restrictions. “For one child, that might mean being able to have two breadsticks at dinner; for another, it mean being able to eat a near-normal diet,” he explained.
“All of these efforts work together to get patients’ phenylalanine levels down and achieve better lifelong compliance,” Dr. Rice concluded.
Given the serious consequences of unmanaged PKU, that is good work indeed.