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Anita MacDonald

Publications and source records attributed to Anita MacDonald.

10 recordsLinked to original sources
PubMed2026

Effect of long-term sepiapterin treatment on dietary phenylalanine tolerance in patients with phenylketonuria: Interim results from the phase 3 APHENITY Extension Study.

PURPOSE: To report interim results from the ongoing, open-label, phase 3 APHENITY Extension Study (NCT05166161), evaluating long-term treatment with sepiapterin in patients with phenylketonuria. METHODS: Participants received an age-based dose of oral sepiapterin daily; those with mean blood phenylalanine (Phe) levels <360 &#x3bc;mol/L (<5.95 mg/dL) after 2 weeks underwent a 26-week dietary Phe tolerance assessment, wherein dietary Phe intake was adjusted and blood Phe levels monitored. Other participants continued treatment with optional diet liberalization. Primary endpoints included change from baseline to week 26 in dietary Phe intake and treatment-emergent adverse events (TEAEs). RESULTS: As of September 2, 2024, 169 participants received sepiapterin (median [minimum, maximum] age: 14.0 [0.2, 55.0] years, median exposure: 72.9 weeks); 102 participants underwent dietary Phe tolerance assessments. Mean (SD) dietary Phe intake increased from 27.6 (18.0) mg/kg/day at baseline to 62.5 (41.5) mg/kg/day at week 26 (least-squares mean change [SE]: 36.4 [2.8] mg/kg/day from baseline) (P < .0001 from post hoc analysis). The incidence of treatment-related TEAEs was 29.0%; 3 participants (1.8%) discontinued treatment owing to treatment-related TEAEs. There were no treatment-related serious TEAEs or deaths. CONCLUSION: Interim results support the long-term safety of sepiapterin and demonstrate the potential for diet liberalization in adults and children with phenylketonuria. GOV IDENTIFIER: NCT05166161 (https://www. CLINICALTRIALS: gov/study/NCT05166161; date of registration, December 8, 2021).

Humans↗
PubMed2025

Global considerations for lifelong management and therapeutic development for phenylketonuria.

Phenylketonuria (PKU) is an inherited metabolic disorder characterized by the accumulation of toxic phenylalanine levels in the brain that can lead to neurocognitive impairment if untreated. This review evaluates unmet needs in PKU, the importance of newborn screening (NBS), and considerations for chronic treatment options. An international group of experts reviewed the available literature across ethnicities and geographies to identify unmet needs of individuals with PKU. Treatment was assessed in a global context to address patient benefit. Reflecting challenges to the worldwide PKU community, some countries have been unable to implement NBS programs and/or do not apply a treatment-for-life approach. Ongoing challenges for individuals with PKU include maintaining adherence to treatment guidelines for patient- and practice-specific reasons, such as inadequate access to low-cost treatment, insufficient social support, limited clinical staffing, and disease burden. Dietary interventions may not adequately address all symptoms, and some of the current pharmacotherapies may be associated with limited efficacy or adverse events. Several new therapies are being evaluated for the treatment of PKU, offering the potential to address unmet needs. Global availability of NBS programs, access to treatments, and a tenacious commitment to treatment-for-life are expected to improve outcomes for individuals with PKU across geographic regions.

Humans↗
PubMed2006

Phenylketonuria: practical dietary management.

Phenylketonuria (PKU) is an autosomal recessively inherited disorder which prevents the normal metabolism of protein foods. Phenylalanine builds up in the blood and if untreated will cause mental retardation. PKU is treatable by a low-phenylalanine diet for life. The prognosis is good provided the condition is diagnosed within the first two weeks of life and dietary treatment started promptly. Special low-phenylalanine formulae and foods are available on prescription in the UK. Supervision by a dietitian and regular monitoring of phenylalanine levels in the blood are essential. The health visitor and school nurse have an important part to play during the school years in supporting the family. Midwives also play an important part in ensuring that women with PKU adhere to a strict low-phenylalanine diet around the time of conception and during pregnancy. They also take blood samples from all newborn babies to be tested for PKU.

Child↗
PubMed2006

Artifacts and pitfalls in myocardial perfusion imaging.

Myocardial perfusion imaging (MPI) is an important imaging modality in the management of patients with cardiovascular disease. MPI plays a key role in diagnosing cardiovascular disease, establishing prognosis, assessing the effectiveness of therapy, and evaluating viability. However, MPI is a complex process, subject to a variety of artifacts and pitfalls, which may limit its clinical utility. These factors may be related to the patient (including unique aspects of the patient's heart), the nuclear medicine equipment, or the actions of the technologist. After reviewing this article, the reader should be familiar with the causes and the effects of these potential artifacts and pitfalls. The reader should develop an understanding of steps to limit these factors, actions to correct them if they do arise and, when necessary, how to incorporate their influence into the interpretation of the study.

Artifacts↗
PubMed2002

The impact of phenylketonuria on folate metabolism.

Several reports indicate that biopterin and folate pathways may interact. We examined folate metabolism in PKU patients where hyperphenylalaninaemia leads to a likely excess of THB. We found an increase in total HPLC determined red cell folate in PKU (p=0.0422): specifically, there was an increase in total formyl-H(4)folate (p=0.0002) and H(4)folate (p< or =0.0001), and decrease in total 5-methyl-H(4)folate in PKU patients. At the level of individual oligo-gamma-glutamyl coenzymes, we found that formyl-H(4)folate polyglutamates were virtually all increased in PKU (p=0.0223, 0.0004, 0.0004, 0.0012, and 0.0008 for di-, tri-, tetra-, penta-, and deca-gamma-glutamyl formyl-H(4)folate coenzymes, respectively). Hcy levels did not differ between clinical groups, indicating that folate dependent-Hcy remethylation is not compromised as a consequence of an altered PKU folate disposition. In nature, pentaglutamyl folates are considered the metabolically favoured coenzymes (optimum K(m) for dependent enzymes). The presented data support this-we found that red cell pentaglutamates gave the best measure of metabolism; pentaglutamyl formyl-H(4)folate increased in PKU (p=0.0012) and related methenyls behaved similarly, while, pentaglutamyl 5-methyl-H(4)folate and pentaglutamyl H(4)folate decreased (p< or =0.0001 and 0.0265, respectively). Furthermore, pentaglutamates showed the best correlations between one-carbon oxidation states of folate, as well as with Hcy (p=0.0003 r=-0.54, 95% CI; -0.724 to -0.272). That PKU might influence folate metabolism in some way is unsurprising: patients with DHPR deficiency accumulate DHB and develop secondary folate deficiency-responsive only to reduced folates, while CSF levels of THB are significantly correlated to monoamines and red cell folate in depression. Further studies to confirm the present findings and to ascertain precisely what mechanism operates in PKU that impacts upon folate homeostasis so profoundly are required.

Biopterins↗