Medical foods for PKU diet enter phase II clinical trials

Mealtimes aren’t quite as enjoyable for people with phenylketonuria (PKU) as they are for the rest of us. Those with this genetic disorder have to get their protein by drinking a foul-tasting amino acid “formula.” At the same time, they must avoid natural proteins—eschewing burgers, ice cream and even regular bread—because they lack the enzyme needed to process phenylalanine, one of the 19 amino acids that comprise protein.

If people with PKU do succumb to the temptation of protein-laden foods, phenylalanine builds up in their bloodstream like a toxin, causing fatigue, anxiety, depression, concentration problems and sometimes brain damage. For expecting mothers, high phenylalanine levels can trigger poor growth, birth defects and developmental delays for the infant.

But now they have a more palatable option—a dietary regimen that features a special protein known as glycomacropeptide (GMP), which is derived from cheese whey and contains only trace amounts of phenylalanine. Today’s availability of GMP medical foods is the result of an eight-year, multi-disciplinary effort led by Denise Ney, a UW-Madison professor of nutritional sciences.

Ney’s team’s work paved the way for Cambrooke Foods, a Boston-based medical foods company, to start manufacturing and selling GMP-based products for people with PKU in 2010. Now, with a grant from the FDA’s Orphan Products Development program, Ney is gearing up to conduct phase II clinical trials of this new nutritional approach, hoping to show that GMP medical foods are a superior option to the traditional amino acid formula.

“My hypothesis is that it’s easier for people with PKU to follow their low-phenylalanine diet if they use GMP medical foods, and that this nutritional approach will result in better control of blood phenylalanine levels and maybe also improved cognitive function [compared to the amino acid formula],” says Ney. “If the study is able to establish this, then it’s my hope that GMP medical foods will become the standard of care for the PKU community.”

GMP is a natural, intact protein, so it tastes like protein. Cambrooke Foods’ BetterMilk—which consists largely of GMP, with some limiting amino acids to make it a complete source of protein—can be mixed with water to form a milk-like beverage or incorporated into fruit smoothies, “chocolate milk” and Alfredo sauce.

“For teenagers and adults who cannot tolerate their amino acid formula, this is a major breakthrough,” says Ney. The company is currently expanding their line of GMP products, with a variety of protein-rich sports drinks, meal replacement bars and puddings in the works.

The FDA’s Orphan Products Development grant program is designed to encourage the development of new safe and effective medical products—including medical foods—for rare diseases or conditions. With only 15,000 people with PKU in the U.S., Ney’s study is a great fit. During the study, 30 subjects with PKU who are currently being cared for by the UW Waisman Center and Children’s Hospital of Boston will consume GMP medical foods for three weeks and—separately—the traditional amino acid formula for three weeks, with a “wash out” period between the two phases. The results will allow Ney and study coordinator Sandra van Calcar, an assistant professor of pediatrics at the UW-Madison School of Medicine and Public Health and their collaborators at the Waisman Center, Children’s Hospital of Boston and the UW Institute for Clinical and Translation Research to compare the blood phenylalanine levels, dietary compliance and cognitive function associated with the two diets.

Ney hopes this study will win over physicians and metabolic dietitians who are still hesitant to prescribe GMP medical foods to their PKU patients. “Some of them want to have more information about safety, about what GMP does to blood phenylalanine levels and so forth, and I respect that,” says Ney. “I think this study will address their concerns.”

Over the years, the national PKU community has supported Ney’s GMP research, providing small grants to keep her work moving forward, including awards from the National PKU Alliance, the Mid-Atlantic Connection for PKU and Allied Disorders and the Tennessee PKU Association.

“Their support tells me how important this work is—how important it is to find a way to improve the PKU diet,” says Ney. “Receiving this FDA grant is a win for the whole PKU community.”