Research

The PKU community’s support has enabled us to provide over 85 grants to date to leading researchers. The grants totaled nearly $6.5 million and are helping to secure advancements in treatment and management of PKU and an eventual cure.

Here’s a snapshot of the 2025 Research Grants awarded:

Novel Approaches to Achieving Permanent Therapeutic Gene Insertion in PAH-Deficient Mice

Cary Harding, M.D., Oregon Health & Science University

Dr. Harding and his lab are working to develop a safe and permanent treatment for PKU using gene insertion. This specific project will examine two novel methods to insert a working copy of the phenylalanine hydroxylase (PAH) gene into the liver cells of a PKU mouse, which serves as a model for human PKU. Because this approach would be inserting a working copy of the gene, it is not specific to certain genetic variants, and it can be applied to any animal without a working copy of PAH. If effective, this project could provide the foundation for clinical studies in gene therapy for PKU.

AI4PKU study: Artificial Intelligence for PKU

Charlotte M.A. Lubout, M.D., University Medical Center Groningen

Dr. Lubout and her team will utilize artificial intelligence (AI) to investigate if machine learning can aid in the management of newborns with PKU. This team will develop a machine learning model based on data from patient charts of newborn babies, inclusive of different disease severities, at two metabolic centers in the Netherlands. The goal of this project is to identify factors leading to variation in Phe levels in infants with PKU and to predict Phe values to provide subsequent diet advice to maintain levels in the recommended range. If this foundational project is successful, the proposed machine learning model can be validated and eventually used to guide diet advice in clinic for infants with PKU.

Defining Protein Requirements in Adults with PKU: Impact of Genotype and Medical Food Intake

Jessica Strosahl, Ph.D., Emory University

Dr. Strosahl and her team propose to provide a more accurate, individualized assessment of protein requirements in adults with PKU by better understanding protein metabolism in PKU. To do this, they will use the indicator amino acid oxidation method, which is a minimally invasive test to determine how much of an amino acid someone actually needs in their diet. Specifically, the goals of this project are to determine the protein requirements in adults with PKU of varying disease severities and investigate how these requirements may change if someone has different amounts of medical food and intact protein. If successful, the data gained from this project could help to update nutrition guidelines and treatment strategies to provide more personalized nutrition recommendations for PKU.

Proficiency in Verbal Discourse: A Proposed Outcome Measure for Clinical Trials in Phenylketonuria (PKU)

Susan Waisbren, Ph.D., Boston Children’s Hospital

Dr. Waisbren and her team plan to establish a tool that can detect changes in neurocognition in people with PKU after changes in treatment. Changes in blood phenylalanine (Phe) is the primary method of determining changes in symptoms after treatment updates, but this often fails to capture the patient-reported outcomes and differences in neurocognition. Therefore, this study team is working to create a tool that can measure these changes in symptoms associated with blood Phe levels. This project is a continuation of a previously NPKUA-funded research project by Dr. Waisbren and her team to use statistical and AI analyses to quantify language expression through the Proficiency in Verbal Discourse tool. The data from this project clearly differentiated adults with PKU from a control comparison group and was significantly corelated with changes in Phe. The goals of the present project are to confirm that this tool distinguishes between people with PKU from a comparison control group, show that within-person changes using this tool correlate with changes in blood Phe and demonstrate that this tool reflects patient-reported perceptions of functioning and quality of life. If successful, this project could be the foundational evidence needed to validate this tool to be used in clinical trials for PKU.

Engineered Native Gut Bacteria for Phenylketonuria Therapy

Amir Zarrinpar, M.D., Ph.D., University of California, San Diego

Dr. Zarrinpar and his team are working to develop a novel therapeutic for PKU that will allow for long-term breakdown of dietary Phe in the gut. This team has examined previous strategies that have used engineered probiotics but were unable to engraft in the intestine long enough to be effective, ultimately making them unsuccessful. This highlights a gap in the understanding of how to achieve persistent colonization of live bacterial therapeutics in the gut. Therefore, the goal of this project is to develop a platform that uses a bacterial enzyme that stably engrafts in the gut and provides sustained enzyme activity to serve as a long-term therapeutic without requiring high-dose administration. To do this, Dr. Zarrinpar’s group will engineer native E. coli strains to express phenylalanine ammonia-lyase (PAL), which is an enzyme that helps to break down Phe. If successful, the results of this project can provide the foundation for a gut-based microbial therapy for PKU and will establish a strategy to engineer long-term therapeutic microbial colonization, which can be applied to other metabolic and rare disease treatments.

See the complete list of NPKUA funded research projects

If you are a PKU researcher interested in applying for funding through the NPKUA Research Grant Program, the 2026-2027 application portal will open in spring 2026.