{"id":"507f57b0-115e-5a30-87d7-836f034139b0","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-pal-clinical","predicate":"lowers","statement":"PRISM studies in 261 adults with PAH deficiency found substantial phenylalanine reductions during induction, titration and maintenance pegvaliase treatment.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"7a14361e-ccc8-5f3b-969f-b3db335aca33","mechanism_event_label":"The bypass can lower blood phenylalanine, but has its own treatment risks.","subject":{"id":"9046d3cd-86ab-59b0-be95-58974ff21a51","slug":"pegvaliase","display_name":"Pegvaliase, PEGylated Anabaena variabilis phenylalanine ammonia lyase","entity_type_key":"drug"},"object":{"id":"53c53d5a-5af6-5901-ba09-bccf1f416178","slug":"human-plasma-phenylalanine","display_name":"Human plasma phenylalanine concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"7a14361e-ccc8-5f3b-969f-b3db335aca33","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-pal-clinical-event","event_type":"observed_relationship","label":"The bypass can lower blood phenylalanine, but has its own treatment risks.","description":"PRISM studies in 261 adults with PAH deficiency found substantial phenylalanine reductions during induction, titration and maintenance pegvaliase treatment.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9046d3cd-86ab-59b0-be95-58974ff21a51","slug":"pegvaliase","display_name":"Pegvaliase, PEGylated Anabaena variabilis phenylalanine ammonia lyase","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"53c53d5a-5af6-5901-ba09-bccf1f416178","slug":"human-plasma-phenylalanine","display_name":"Human plasma phenylalanine concentration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"190407ad-0219-54b5-b05f-7c75f3895ca6","slug":"l-phenylalanine","display_name":"L-Phenylalanine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Adult phase-3 clinical program with long-term titrated exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Immune-mediated adverse events matter: 17 events in 12 participants met acute systemic hypersensitivity/anaphylaxis criteria. This is not dietary enzyme use.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-phenylalanine","display_name":"L-Phenylalanine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The bypass can lower blood phenylalanine, but has its own treatment risks.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Pegvaliase for the treatment of phenylketonuria: Results of a long-term phase 3 clinical trial program (PRISM). · 2018 · https://pubmed.ncbi.nlm.nih.gov/29653686/ · DOI 10.1016/j.ymgme.2018.03.006","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"5669af3b-6fa7-52ef-8c53-ab86b0f89537","evidence_kind":"source_excerpt","locator":"Lines 246-252","start_line":246,"end_line":252,"excerpt":"## l-phenylalanine-pal-clinical\nThe bypass can lower blood phenylalanine, but has its own treatment risks.\nPRISM studies in 261 adults with PAH deficiency found substantial phenylalanine reductions during induction, titration and maintenance pegvaliase treatment.\nModel: Adult phase-3 clinical program with long-term titrated exposure.\nLimitations: Immune-mediated adverse events matter: 17 events in 12 participants met acute systemic hypersensitivity/anaphylaxis criteria. This is not dietary enzyme use.\nEvidence access: Primary abstract\nPegvaliase for the treatment of phenylketonuria: Results of a long-term phase 3 clinical trial program (PRISM). · 2018 · https://pubmed.ncbi.nlm.nih.gov/29653686/ · DOI 10.1016/j.ymgme.2018.03.006","model_system":"Adult phase-3 clinical program with long-term titrated exposure.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"54de7c56-1e60-5d7b-8ef9-852c58ae92ba","stable_key":"import-56f1d914-e7da-595a-af69-c217b2b47407","title":"L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"4d53adcd4acc7a9aecf44ccb2623ec540c9d221a0f7c00002585870b39b8ffb8","revision_id":"fd182a81-4ab7-559a-9c77-fb4cf72982ef","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}