Publications by authors named "R T Zori"
Article Synopsis
- Phenylketonuria (PKU) is a genetic condition where too much phenylalanine (Phe) builds up in the body, which can be harmful to the brain.
- The APHENITY study tested a new medicine called synthetic sepiapterin to see if it could safely lower Phe levels in patients with PKU.
- The study involved 187 participants from 34 locations around the world and lasted from September 2021 to April 2023, with results showing how effective the treatment was over a six-week period.
Article Synopsis
- - Phenylketonuria (PKU) is a genetic disorder that leads to dangerous levels of phenylalanine in the blood due to a deficiency in the enzyme phenylalanine hydroxylase, requiring ongoing treatment to maintain safe levels.
- - Pegvaliase is an approved enzyme-substitution therapy for patients with uncontrolled PKU, showing significant reductions in blood phenylalanine levels in clinical trials, although individual responses to treatment and required doses can vary.
- - In a study with 261 adults on pegvaliase treatment for an average of 36.6 months, many participants achieved clinically significant reductions in blood phenylalanine levels, and long-term safety data indicated common side effects like joint pain and injection
Phenylketonuria is characterized by intellectual disability and behavioral, psychiatric, and movement disorders resulting from phenylalanine (Phe) accumulation. Standard-of-care treatment involves a Phe-restricted diet plus medical nutrition therapy (MNT), with or without sapropterin dihydrochloride, to reduce blood Phe levels. Pegvaliase is an injectable enzyme substitution treatment approved for adult patients with blood Phe >600 μmol/L despite ongoing management.
View Article and Find Full Text PDFDespite available treatment options, many patients with phenylketonuria (PKU) cannot achieve target plasma phenylalanine (Phe) levels. We previously modified Escherichia coli Nissle 1917 to metabolize Phe in the gut after oral administration (SYNB1618) and designed a second strain (SYNB1934) with enhanced activity of phenylalanine ammonia lyase. In a 14-day open-label dose-escalation study (Synpheny-1, NCT04534842 ), we test a primary endpoint of change from baseline in labeled Phe (D5-Phe AUC; D5-Phe area under the curve (AUC) over 24 hours after D5-Phe administration) in plasma after D5-Phe challenge in adult participants with screening Phe of greater than 600 µM.
View Article and Find Full Text PDFClinical trial development in rare diseases poses significant study design and methodology challenges, such as disease heterogeneity and appropriate patient selection, identification and selection of key endpoints, decisions on study duration, choice of control groups, selection of appropriate statistical analyses, and patient recruitment. Therapeutic development in organic acidemias (OAs) shares many challenges with other inborn errors of metabolism, such as incomplete understanding of natural history, heterogenous disease presentations, requirement for sensitive outcome measures and difficulties recruiting a small sample of participants. Here, we review strategies for the successful development of a clinical trial to evaluate treatment response in propionic and methylmalonic acidemias.
View Article and Find Full Text PDF