Phenylketonuria

This trial is intended to understand how the body processes repinatrabit in people with moderate liver impairment and severe kidney impairment and also to compare these results with people of similar age, weight, and sex who have normal liver function.

The primary purpose of this study is to assess the safety and tolerability of AG-181 in subjects with Phenylketonuria (PKU).

The main purpose of this trial is to evaluate the long-term efficacy of sepiapterin on preserving neurocognitive functioning in children with PKU when treatment is initiated in early childhood.

Phenylketonuria (PKU) is an inherited disorder of phenylalanine (Phe) metabolism. The mainstay of treatment is a Phe-restricted diet, which aims to maintain blood Phe concentrations within the recommended range and prevent neurological complications. Some individuals with PKU respond to pharmacological treatments, including sapropterin, a synthetic form of tetrahydrobiopterin (BH4), or sepiapterin. These treatments may increase Phe tolerance and allow a less restrictive diet. Diet is an important determinant of gut microbiota composition and function. However, the effects of the Phe-restricted diet and pharmacologically enabled dietary relaxation on the gut microbiota in PKU remain poorly understood. This observational study includes children and adolescents with PKU aged 3-17 years attending Birmingham Children's Hospital. Participants include those managed exclusively with a Phe-restricted diet, those receiving sapropterin, and those receiving sepiapterin. One healthy household control is recruited for each participant with PKU. Faecal samples are collected for shotgun metagenomic sequencing and metabolite profiling. Dietary intake, gastrointestinal symptoms, stool characteristics, clinical information, and PKU treatment are also assessed. The study investigates whether gut microbiota composition, microbial functional potential, and faecal metabolite profiles differ between participants managed with a Phe-restricted diet, those receiving pharmacological treatment, and healthy household controls. The findings may improve understanding of the relationships between PKU treatment, dietary restriction, gastrointestinal health, and the gut microbiome and may inform future nutritional strategies for individuals with PKU.

The prevalence of eating disorders and BMI are significantly higher in PKU patients than in the general population. The protein-restricted diet associated with high carbohydrate intake and the severity of the genetic defect and disease can lead to weight gain in these patients; However, the link between restrictive diets, EDs, and obesity has not been demonstrated in patients with PKU. These issues remain poorly explored, meaning that patients may not be detected and treated.

The goal of this Phase 3, randomized study is to assess the safety, efficacy, tolerability, and pharmacokinetics (PK) of oral JNT-517 in adults (18 years of age or older) with PKU. Participants will receive either JNT-517 or placebo and will be blinded to their treatment assignment. Participants will have a 2 in 3 (or approximately 67%) chance of receiving JNT-517 during the first part of the study which will last approximately six weeks. During the second part of the study every participant who continues in the study will receive one of two doses of JNT-517 for an additional 46 weeks. The study requires a screening period of up to 35 days to ensure dietary stabilization and amino acid levels required to meet study eligibility. In total, participation in the study could last for up to 400 days. Participants will: Take 75 mg JNT-517 or 150 mg JNT-517, or a placebo BID (2x per day) for approximately 365 days; Visit the clinic or have a mobile health nurse visit your home for checkups and tests; Collect urine sample at home and bring to clinic on specified days; Keep a food diary 3 days before each study visit

This study is a Phase I single ascending dose clinical trial in which healthy adult volunteers were administered single oral doses of GenSci144 tablets at different levels. It was conducted using a randomized, double-blind, placebo-controlled design, primarily to evaluate the drug's safety and tolerability, while also exploring its pharmacokinetic and pharmacodynamic characteristics in the body, providing a basis for subsequent clinical use in the treatment of phenylketonuria.

The aims of this collaborative, interdisciplinary research project are to understand and describe the psychological impact of the announcement of a rare, serious disease present since birth and detected in the context of the systematic neonatal screening (DNS), in terms of the parents' experience, but also on the part of the medical team, in order to improve its process and the support it provides for the announcement of the diagnosis.

Study 165-401 is a Phase 4, open-label study designed to examine the concomitant use of methotrexate (MTX) to suppress immune responses to Palynziq and improve tolerability and efficacy in adults with PKU.

The purpose of this project is to study the effectiveness of teaching teens and young women with Phenylketonuria (PKU) or Maple Syrup Urine Disease (MSUD) about their disease and nutrition related issues in a camp environment. It will also look at pregnancy outcome results in women with PKU who attended Metabolic Camp and compare their results to other women with PKU who have not attended the Metabolic Camp.

This study will be the first in the literature to evaluate the relationship between aerobic and resistance exercises, plasma amino acid levels, metabolic control of patients, and the metabolic response to exercise with different types of meals in patients with Phenylketonuria (PKU). In patients with phenylketonuria, the aim is to determine which pre-exercise dietary recommendations are more physiologically appropriate and ideal for achieving good metabolic control. In the literature, there are very few studies examining the effects of exercise on plasma amino acid levels and metabolic parameters in PKU patients.

Four new GMP-based protein substitutes have been developed to support the dietary management of PKU and TYR. These products are powdered protein substitutes, low in phenylalanine and low in phenylalanine and tyrosine respectively, with a mix of glycomacropeptide (GMP), essential and non-essential amino acids, carbohydrates, fibres, fats (including DHA) and micronutrients. The proteins in these new protein substitutes are based on GMP, a peptide isolated from milk during cheese manufacturing and the only known naturally derived protein source low in phenylalanine and tyrosine. The GMP is supplemented with other amino acids which are naturally low or not present in GMP, as well as carbohydrates, fats, fibre and micronutrients. Studies to date have illustrated that PKU patients who replace their regular phenylalanine-free amino acid-based formula with GMP-based foods may have better diet compliance and prefer the taste whilst maintaining metabolic control. This series of case-studies aims to evaluate the gastrointestinal tolerance, acceptability, compliance, and safety of these four GMP based protein substitutes in both adults and children over 3 years. These case studies will last 29 days in total, including a 1-day baseline period followed by a 28-day intervention period. The case studies will be conducted across multiple specialist metabolic centres in the UK. A series of case studies is undertaken due to the rarity of these conditions, the diversity of patient types and the difficulty in recruiting these patients to trials.