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Drug frees PKU patients from restrictive diet | Overview

Children with phenylketonuria (PKU) must have all their foods weighed and measured to minimize their intake of phenylalanine (phe), lest it accumulate and cause brain damage. Results from an international study led by Boston Children's Hospital however suggest that some patients can lower their phenylalanine levels with a drug called BH4 (tetrahydrobiopterin), potentially allowing them to ease up on their strict, very low protein diet.

BH4 boosts the action of phenylalanine hydroxylase (PAH), the enzyme that breaks down phe, which is defective in patients with PKU. But BH4 doesn't work in everyone. "Some patients have such a severe genetic defect that they don't even make PAH, or the enzyme is so deformed that it doesn't function," notes Harvey Levy, MD, director of the Maternal PKU Program at Boston Children's.

The Phase III trial, published in Lancet, randomized 89 BH4 "responders" (patients with a 30 percent or greater drop in blood phe levels in a pilot study) received either BH4 or a placebo. All patients were asked to continue their PKU diets. After six weeks, 54 percent of the BH4 group, versus 23 percent of the placebo group, had phe levels in the desired range (compared with 17 and 19 percent, respectively, before treatment).

The drug approved by the FDA in 2008, and now marketed as Kuvan, is the first and only therapeutic available specifically for the treatment of PKU.

"We recommend that all children and adults with PKU be tested for BH4 responsiveness," says Levy. "But we don't yet know how clinically significant the phe reduction is, or whether patients will continue to respond to BH4 as they get older."