Below is a brief synopsis of work being done by leading researchers across the country to improve PKU treatment options.

In January, 2010 the Molecular Genetics and Metabolism scientific journal published a supplement on PKU and the Brain. Since then, other new research findings have also been published on PKU and neurocognitive effects. To learn more about this groundbreaking research of PKU in neurocognitive development, executive function, and psychology in patient-friendly language, please click here.

The first drug for PKU was approved by the FDA in December 2007. Kuvan, improves Phe tolerance in some PKU patients by increasing BH4 in the body, the co-factor to the PAH enzyme that does not work in those with PKU. Kuvan essentially stimulates the PAH enzyme, which in turn starts to process Phe. While Kuvan does not replace the diet, it can improve Phe tolerance in about 40% of PKU patients. There is currently no genotype indicator for Kuvan responsiveness, so a physician must put a person with PKU on the drug for a trial period to evaluate its effectiveness.

To learn the latest published research on recommendations related to Kuvan, please 
click here

In enzyme substitution, researchers discovered an alternate enzyme found in plants and bacteria that can breakdown Phe. In order for the enzyme to work, a protector, or “coater” needs to be placed around the enzyme to help it from breaking down quickly in the body and protecting the enzyme from the immune response. The result, is Pegvaliase, an injectible medicine that has shown to lower Phe levels. In Phase 2 FDA clincial studies, 23 adult patients enrolled in the study for an average of 111 days. All patients in the study experienced a decrease in blood phenylalanine levels. 

BioMarin recently completed Phase 3 Trial for Pegvaliase. Results of the trial can be found here.

LNAA’s also shows promising results to treat people with PKU. Essentially, LNAA’s compete with Phe for transport into the brain. By introducing other LNAA’s in the diet, the passage of Phe is blocked to the brain, thereby decreasing brain Phe levels. There are currently four products available: Lanaflex, PreKUnil, NeoPhe and PheBloc. LNAA’s do not replace the diet, but they may be good adjunct therapy for those who have a poorly controlled diet.

Glycomacropeptide (GMP) is a whey-based protein that is produced when making cheese. It is the only known dietary protein that contains a minimal amount of Phe. Foods made with GMP provide an alternative to the amino acid medical foods currently required in the PKU diet. GMP foods have also been found to significantly lower Phe levels in blood and plasma. Some GMP-containing products are already on the market for PKU, such as BetterMilk.

Click here to read a publication about the GMP diet with PKU mice.


Gene therapy is an ideal treatment for treating PKU because it would be able to transfer a functional PAH enzyme into the liver cells. Unfortunately, the challenge in gene therapy has been the immune response. While gene therapy has worked in curing PKU in mice, immunosuppressant medications have also had to be used to maintain the correction. Some new techniques have shown promise though, including recombinant adenovirus-associated vectors (rAAV), and using a heterologous tissue approach. rAAV’s have been shown to cause less immune response, maintain a longer correction and be safer. Current research includes injecting rAAV’s into the muscle versus the liver.


Since liver cells in PKU patients are deficient in PAH, this promising line of research involves replacing some of the defective liver cells with cells that have normal PAH activity (either from donor livers or through stem cells). The procedure is non-invasive, and involves infusing cells through the umbilical vein (belly button), which leads into the portal vein and finally the liver. Transplantation of hepatocytes (the primary cell in liver) has been used in other inborn errors of metabolism diseases, and is currently in clinical trial at the Children’s Hospital of Pittsburgh where one PKU patient has already been transplanted with encouraging results. Unfortunately, the main drawbacks of hepatocytes are limited availability of donor livers for cell isolation and the need for immunosuppression. However, stem cells isolated from full term human placenta (human amnion epithelial cells, or hAEC) are plentiful, safe, and have special properties allowing them to evade immune detection making immunosuppression unnecessary. Based on strong preclinical data showing significant corrections of MSUD and PKU mice, approval was granted to begin isolation and banking of hAEC under GMP procedures at Karolinska Institutet, and to perform hAEC transplants on up to 10 patients with liver diseases where hepatocyte transplant would be considered. 

Click here for the hepatocyte transplantation clinical trial page.

Click here to see the scientific posters recently presented on PKU at the 2015 Society for Inherited Metabolic Disorders meeting.

Click here for Self-Management Skills and Treatments Knowledge in Patients with Phenylketonuria.

These are just a few of the many exciting advances in PKU research. The NPKUA is leading the effort to raise and distribute funds.