July 13, 2016
Food products made from a specific protein found in whey can safely be part of a more palatable diet for individuals diagnosed with phenylketonuria (PKU), according to a new clinical trial led by researchers at the University of Wisconsin—Madison and Boston Children’s Hospital.
|Denise Ney, PhD
“Our findings could also lead to increased insurance coverage for ‘medical foods’ that individuals with PKU need to lead healthy lives,” says Denise Ney, the lead author of the study. Ney is a professor of nutritional sciences in the College of Agricultural and Life Sciences at UW–Madison and a researcher at the UW’s Waisman Center.
PKU is a rare disease. It affects approximately 15,000 people in the United States. Individuals with PKU cannot metabolize the amino acid phenylalanine. If left untreated, PKU can lead to the accumulation of dangerous levels of the amino acid in the body, which can cause intellectual disabilities, seizures and other serious health problems.
There is no cure for PKU and individuals diagnosed with it find themselves in a double bind. The only way to manage the disease is to adhere strictly to a diet low in phenylalanine throughout life. But almost all naturally occurring proteins contain phenylalanine, and having to avoid it makes it very difficult for individuals with PKU to consume enough protein.
Traditionally, synthetic protein substitutes made from mixtures of amino acids have been used to create nutritional formulas that PKU patients need to drink daily to ensure they get enough protein in their diets. These protein substitutes can only be consumed as a formula, tablets or gel and cannot be made into other food products such as bars or spreads.
“Also, they are often described as ‘smelling bad and tasting worse’ and it can be difficult for adults, let alone children, to stick to this diet day after day,” says Ney.
To overcome some of the shortcomings of the synthetic protein diet, Ney has worked to develop safer and more palatable options for PKU patients. She focused on a protein called glycomacropeptide (GMP), a natural leftover in the whey created during production of cheese.
Participants in the study rated the GMP foods as more palatable — which could increase how strictly PKU patients stick to their diets.
GMP is unusual in that it is the only known natural protein that contains no phenylalanine in its pure form. The small amounts of the amino acid in food products made using GMP come from other proteins left over from the process used to purify GMP from whey.
Harry Waisman with a patient who was diagnosed with PKU two weeks after birth and put on a low phenylalanine diet. She went on to avoid the dramatic consequences of the metabolic disease and developed typically. Photo courtesy of Waisman Center
After promising results using animal models and a prior clinical trial to establish the safety of GMP medical foods, Ney and her colleagues in Boston initiated a clinical trial, which followed 30 individuals with PKU over several weeks.
The results showed that trial participants who consumed GMP foods had similar levels of phenylalanine in their blood as participants who consumed the traditional amino acid formula, even though GMP foods contain more phenylalanine than the synthetic amino acids.
They also rated the GMP foods as more palatable — which could increase how strictly PKU patients stick to their diets — and showed fewer negative side effects, such as persistent hunger and gastrointestinal symptoms, compared to participants who were on the traditional synthetic amino acid diet.
“We provide evidence that GMP medical foods provide a safe and acceptable alternative to synthetic formulas for managing PKU,” says Ney.
Medical foods made using GMP are currently more expensive than the traditional amino acid formula, but Ney believes that with wider usage and adoption of the new foods, the price difference will diminish.
Screening and management of PKU has a long and storied connection to Wisconsin. Harry Waisman, a researcher and clinician — after whom the Waisman Center is named — was instrumental in initiating the testing of infants for PKU and treating individuals with the disorder throughout the state.
“I think this research exemplifies the Wisconsin Idea — developing a way to better manage a disease that cuts across demographics and nationalities using a byproduct of cheese production,” says Ney.
Funding for this research was provided by the Office of Orphan Products Development of the U.S. Food and Drug Administration and the National Center for Advancing Translational Sciences. Ney is a co-inventor of the GMP medical foods used in the clinical trial, the patent on which is held by the Wisconsin Alumni Research Foundation (WARF) and licensed to Cambrooke Therapeutics.