Long-Term Metabolic Correction of Phenylketonuria by AAV-Delivered Phenylalanine Amino Lyase
نویسندگان
چکیده
منابع مشابه
A different approach to treatment of phenylketonuria: phenylalanine degradation with recombinant phenylalanine ammonia lyase.
Phenylketonuria (PKU), with its associated hyperphenylalaninemia (HPA) and mental retardation, is a classic genetic disease and the first to have an identified chemical cause of impaired cognitive development. Treatment from birth with a low phenylalanine diet largely prevents the deviant cognitive phenotype by ameliorating HPA and is recognized as one of the first effective treatments of a gen...
متن کاملLong-term beneficial effects of the phenylalanine-restricted diet in late-diagnosed individuals with phenylketonuria.
The potential benefits to society of treating late-diagnosed mentally retarded persons with phenylketonuria were investigated. In order to ascertain the effects of late dietary intervention, the charts of 124 adults with PKU seen in the metabolic service at the Childrens Hospital of Los Angeles were reviewed. Fifty-nine were diagnosed later than 3 months of age and were over the age of 18 years...
متن کاملPhenylalanine Metabolism: Phenylketonuria
The hydroxylase is a trimer of approximately 150 kDa of identical subunits and is located predominantly in the liver. The enzyme has been mapped to human chromosome 12q22-24.1, where the gene comprises 13 exons extending over 90 kb of genomic DNA. Deletions in the gene are not common. A frequent cause among northern Europeans (~40%) is a G-to-A transition at the 5′ donor splice site in intron 1...
متن کاملLong-term treatment with tetrahydrobiopterin increases phenylalanine tolerance in children with severe phenotype of phenylketonuria.
Hyperphenylalaninemia caused by phenylalanine hydroxylase (PAH) deficiency requires lifelong rigorous diet starting in early infancy to prevent severe neurodevelopmental handicap. In a considerable number of children with mild hyperphenylalaninemia, long-term tetrahydrobiopterin (BH4) treatment significantly improves phenylalanine (phe) tolerance, but it has never been investigated in classic p...
متن کاملPreclinical evaluation of multiple species of PEGylated recombinant phenylalanine ammonia lyase for the treatment of phenylketonuria.
Phenylketonuria (PKU) is a metabolic disorder, in which loss of phenylalanine hydroxylase activity results in neurotoxic levels of phenylalanine. We used the Pah(enu2/enu2) PKU mouse model in short- and long-term studies of enzyme substitution therapy with PEGylated phenylalanine ammonia lyase (PEG-PAL conjugates) from 4 different species. The most therapeutically effective PAL (Av, Anabaena va...
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ژورنال
عنوان ژورنال: Molecular Therapy - Methods & Clinical Development
سال: 2020
ISSN: 2329-0501
DOI: 10.1016/j.omtm.2019.12.014