Research

The PKU community’s support has enabled us to provide 76 grants to date to leading researchers. The grants totalled over $5 million and are helping to secure advancements in treatment and management of PKU and an eventual cure.

Here’s a snapshot of the 2024 Research Grants awarded:

Development of Novel Psychological Assessment Tools & Anxiety Intervention for PKU
Shawn E. Christ, Ph.D., University of Missouri

The focus of this research is to explore the efficacy and feasibility of a short-term skills-based intervention (Show ME FIRST) on anxiety and depression in adolescents with PKU. Additionally, this team plans to assess the validity of a novel assessment tool created by their research team to capture real time neurocognitive and psychological function.

Cell Therapy for Phenylketonuria
Markus Grompe, M.D., Oregon Health & Sciences University

The research to be conducted will explore methods of overcoming two current challenges with hepatocyte transplantation as a cure for PKU: insufficient cell replacement levels to achieve correction of systemic phenylalanine levels, and issues related to immunosuppression. To combat insufficient cell replacement levels, their team has developed a system of cell expansion via gene-edited hepatocytes that are resistant to the hepatotoxic effects of the drug acetaminophen. These gene-edited hepatocytes will preferentially expand over the non-gene edited cells that are not resistant to acetaminophen toxicity. This approach has proven to provide long-lasting therapeutic correction of blood phenylalanine levels in a PKU mouse model. Secondly, their team plans to generate immune stealthy hepatocytes to prevent immune rejection in allogenic hepatocyte transplantation.

Structural Insights into the Regulation of Phenylalanine Hydroxylase in Phenylketonuria
Kushol Gupta, Ph.D., University of Pennsylvania

This research aims to gain a detailed mechanistic understanding of the regulation of the PAH enzyme by creating a synthetic version of two PAH gene mutations that can rescue the mutated PAH enzyme increasing its enzymatic activity. They hope this will allow for a determination of the molecular basis of allosteric regulation of the PAH enzyme and a better understanding of how clinical mutations affect PAH enzyme regulation. This approach can potentially lead to development of future treatments for PKU.

Novel Approaches to Achieving Permanent Gene Correction in PAH-Deficient Mice
Cary O. Harding, M.D., Oregon Health & Sciences University

This research aims to investigate the therapeutic effectiveness of two possible approaches in a PAH-deficient mouse model of human PKU: CRISPR-Cas9 facilitated gene integration of a phenylalanine hydroxylase (PAH) gene into the hepatocyte genome of PAH-deficient mice, or a novel gene editing strategy called Programmable Addition via Site-specific Targeting Elements (PASTE) that could improve the frequency of gene editing.

Can Care of Adult PKU Be Improved with Additional Dietary Large Neutral Amino Acids: A Protocol for an Nof-1 Study
Shoji Yano, M.D., Ph.D., University of Southern California,

This research will use Phenylalanine (Phe), Tyrosine (Tyr), and the Phe/Tyr ratio as biomarkers, as well as other clinical assessments to determine the impact of large neutral amino acids (LNAAs) on the outcomes of PKU adults. LNAAs have historically been used as a treatment to reduce the amount of Phe that can be taken up by the brain through competition with other neutral amino acids across the LATI transporter. Their team hopes to identify the appropriate use of LNAAs to improve neurocognitive symptoms and possibly allow increased dietary protein intake. This study was previously awarded grant funding from the NPKUA but has requested additional funds to increase enrollment in hopes of providing more definitive study results.

Download Research Grant PDF