Safety and pharmacodynamics of an engineered E. coli Nissle for the treatment of phenylketonuria: a first-in-human phase 1/2a study.
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
17
02
2021
accepted:
23
06
2021
pubmed:
24
7
2021
medline:
5
10
2021
entrez:
23
7
2021
Statut:
ppublish
Résumé
Phenylketonuria (PKU) is a rare disease caused by biallelic mutations in the PAH gene that result in an inability to convert phenylalanine (Phe) to tyrosine, elevated blood Phe levels and severe neurological complications if untreated. Most patients are unable to adhere to the protein-restricted diet, and thus do not achieve target blood Phe levels. We engineered a strain of E. coli Nissle 1917, designated SYNB1618, through insertion of the genes encoding phenylalanine ammonia lyase and L-amino acid deaminase into the genome, which allow for bacterial consumption of Phe within the gastrointestinal tract. SYNB1618 was studied in a phase 1/2a randomized, placebo-controlled, double-blind, multi-centre, in-patient study ( NCT03516487 ) in adult healthy volunteers (n = 56) and patients with PKU and blood Phe level ≥600 mmol l
Identifiants
pubmed: 34294923
doi: 10.1038/s42255-021-00430-7
pii: 10.1038/s42255-021-00430-7
doi:
Substances chimiques
Amidohydrolases
EC 3.5.-
Phenylalanine Ammonia-Lyase
EC 4.3.1.24
Banques de données
ClinicalTrials.gov
['NCT03516487']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1125-1132Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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