TY - JOUR
T1 - White matter integrity and executive abilities following treatment with tetrahydrobiopterin (BH4) in individuals with phenylketonuria
AU - White, Desirée A.
AU - Antenor-Dorsey, Jo Ann V.
AU - Grange, Dorothy K.
AU - Hershey, Tamara
AU - Rutlin, Jerrel
AU - Shimony, Joshua S.
AU - McKinstry, Robert C.
AU - Christ, Shawn E.
N1 - Funding Information:
This research was supported by an Investigator Sponsored Trial grant from BioMarin Pharmaceutical Inc. This research was also supported by a grant from the National Institute on Drug Abuse ( T32DA007261 ) and the Human Clinical Core of the Washington University Intellectual and Developmental Disabilities Research Center which is funded by the National Institute of Child Health and Human Development ( P30HD062171 ) and the James S. McDonnell Foundation . Drs. White and Christ serve as consultants to BioMarin Pharmaceutical Inc., and Dr. White serves as a consultant to Merck Serono S.A., but the content of this article has not been influenced by these relationships. The authors thank those who participated in our study for their contributions to our research. We also thank Suzin Blankenship and Laurie Sprietsma for their contributions to study management, as well as the physicians, faculty, and staff of Washington University, University of Missouri, University of Florida, St. Louis University, New York Medical College, and University of Nebraska who generously contributed through recruitment and phenylalanine monitoring.
Funding Information:
The research detailed in the article was supported by an Investigator Sponsored Trial grant from BioMarin Pharmaceutical Inc. Drs. White and Christ serve as consultants to BioMarin Pharmaceutical Inc., and Dr. White serves as a consultant to Merck Serono S.A., but the content of this article has not been influenced by these relationships.
PY - 2013/11
Y1 - 2013/11
N2 - Tetrahydrobiopterin (BH4) lowers blood phenylalanine (Phe) in individuals with PKU who are responders, but its effects on the brain and cognition have not been explored thoroughly. We examined blood Phe, microstructural white matter integrity, and executive abilities in 12 BH4 responders before (i.e., baseline) and after (i.e., follow-up) six months of treatment with BH4. Compared with baseline, Phe in these responders decreased by 51% during a 4week screening period after initiation of treatment and remained lowered by 37% over the 6month follow-up period. Significant improvements in white matter integrity, evaluated by mean diffusivity from diffusion tensor imaging, were also found following six months of treatment. Improvements in executive abilities were not identified, although six months may have been a period too brief for changes in cognition to follow changes in the brain. To our knowledge, our study is the first to explore relationships among Phe, white matter integrity, executive abilities, and BH4 treatment within a single study.
AB - Tetrahydrobiopterin (BH4) lowers blood phenylalanine (Phe) in individuals with PKU who are responders, but its effects on the brain and cognition have not been explored thoroughly. We examined blood Phe, microstructural white matter integrity, and executive abilities in 12 BH4 responders before (i.e., baseline) and after (i.e., follow-up) six months of treatment with BH4. Compared with baseline, Phe in these responders decreased by 51% during a 4week screening period after initiation of treatment and remained lowered by 37% over the 6month follow-up period. Significant improvements in white matter integrity, evaluated by mean diffusivity from diffusion tensor imaging, were also found following six months of treatment. Improvements in executive abilities were not identified, although six months may have been a period too brief for changes in cognition to follow changes in the brain. To our knowledge, our study is the first to explore relationships among Phe, white matter integrity, executive abilities, and BH4 treatment within a single study.
KW - Diffusion tensor imaging
KW - Executive
KW - Phenylketonuria
KW - Sapropterin
KW - Tetrahydrobiopterin
KW - White matter
UR - http://www.scopus.com/inward/record.url?scp=84885431162&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2013.07.010
DO - 10.1016/j.ymgme.2013.07.010
M3 - Article
C2 - 23928118
AN - SCOPUS:84885431162
SN - 1096-7192
VL - 110
SP - 213
EP - 217
JO - Molecular genetics and metabolism
JF - Molecular genetics and metabolism
IS - 3
ER -