Biomedical subjects

Nicola Longo

Publications and source records attributed to Nicola Longo.

3 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 μmol/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

Pathogenic XPO1 variants cause a dominant neurodevelopmental disorder.

PURPOSE: XPO1 functions in key cellular processes, including nucleo-cytoplasmic export and mitosis. The gene is deleted in a subset of patients with the 2p15p16.1 microdeletion syndrome; however, no monogenic XPO1-related disorder has been described to date. METHODS: We collected clinical data of individuals with de novo XPO1 variants through online matchmaking. We used Drosophila to study XPO1 function in development and habituation learning. RESULTS: A total of 22 individuals met the criteria to be included in the main study cohort. Of these, half have putative loss-of-function variants, and half have coding variants (10 missense and 1 in-frame deletion variant). We found an overlapping phenotype, consistent with a monogenic neurodevelopmental disorder. We demonstrate XPO1 functions in development by ubiquitous and neuron-specific knockdown in Drosophila. GABAergic neuron specific knockdown flies demonstrated impaired habituation. CONCLUSION: Our results establish XPO1 as a novel dominant monogenic neurodevelopmental disorder gene and demonstrate a central role for XPO1 in development.

Exportin 1 Protein↗

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↗