Sepiapterin modulation on neurobehavioral phenotypes and peripheral markers in hyperphenylalaninemia | Fondazione Santa Lucia

Sepiapterin modulation on neurobehavioral phenotypes and peripheral markers in hyperphenylalaninemia

The Project combines preclinical and clinical study to assess if tetrahydrobiopterin (BH4) and sepiapterin (the precursor of BH4) treatment improve brain functioning in hyperphenylalaninemia (HPA) by stimulating brain neurotransmitter synthesis. 

We investigate the effects of BH4 administration in mice modeling different degree of HPA, including PKU, on brain neurotransmitters and their metabolites, on peripheral metabolites, and on behavioral and cognitive tests, and in HPA patients with different levels of HPA to assess peripheral metabolites and neurocognitive abilities. Moreover, the effects of the BH4 precursor sepiapterin in the animal models will be compared with those of BH4.  

In particular we assess: 1) the effects of BH4 and sepiapterin administration in mice modeling different degree of HPA, including PKU, on brain and CSF neurotransmitters and their metabolites, on peripheral (plasma) metabolites, and on behavioral and cognitive tests; and 2) the effect of BH4 (Sapropterin; Kuvan) in BH4-responsive HPA patients with different levels of HPA to assess peripheral metabolites and neurocognitive abilities; 3) the effects of the BH4 precursor sepiapterin in the preclinical model to compare its effects with those of BH4 on the same neurochemical and behavioral tests.

Research Unit 
Neurobiology of Behavior Lab
Project Duration 
12/2015 - 05/2017
Partner 
  • Università degli Studi di Roma Sapienza - Project Coordinator
  • University of Groningen, Groningen (Netherlands)