A new whey to treat a rare disease

Shortly after birth, most babies are screened using the ‘heel prick test’, which tests for rare metabolic disorders. One of the conditions identified by the blood test is phenylketonuria (PKU), a rare disease affecting approximately 15,000 people in the United States.

Individuals with PKU cannot metabolise 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; the only way to manage the disease is to adhere strictly to a diet low in phenylalanine. However, almost all naturally occurring proteins contain phenylalanine, so individuals with PKU can struggle to consume enough protein.

Traditionally, synthetic protein substitutes made from mixtures of amino acids have been used to create nutritional formulas for PKU patients, but these are often unpalatable, making it challenging to consume them every day.

Now, a clinical trial led by researchers at the University of Wisconsin-Madison and Boston Children’s Hospital has found that food products made from a specific protein found in whey can safely be part of a more palatable diet for individuals diagnosed with PKU.

Denise Ney, the lead author of the study, focused on a protein called glycomacropeptide (GMP), a natural leftover in the whey created during production of cheese.

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.

After promising results using animal models and a prior clinical trial to establish the safety of GMP medical foods, Ney and her colleagues 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.

Participants 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,” said Ney.

Image caption: Lead author of the study, Denise Ney.