The Newborn Screening Programme Revisited: An Expert Opinion on the Challenges of Rett Syndrome DOI Open Access
Jatinder Singh, Paramala Santosh

Genes, Journal Year: 2024, Volume and Issue: 15(12), P. 1570 - 1570

Published: Dec. 5, 2024

Genomic sequencing has the potential to revolutionise newborn screening (NBS) programmes. In 2024, Genomics England began recruit for Generation Study (GS), which uses whole genome (WGS) detect genetic changes in 500 genes more than 200 rare conditions. Ultimately, its purpose is facilitate earlier identification of conditions and thereby improve health-related outcomes individuals. The adoption into GS was guided by four criteria: (1) gene causing condition can be reliably detected; (2) if undiagnosed, would have a serious impact; (3) early or presymptomatic testing substantially outcomes; (4) interventions screened are accessible all. Rett syndrome (RTT, OMIM 312750), paediatric neurodevelopment disorder, not included list GS. this opinion article, we revisit discuss RTT from perspective these criteria. We begin with an introduction then summarise key points about principles, presenting challenges opportunities individuals RTT. provide insight how data could collected during phase, diagnosis our understanding prodromal stage Although many features present departure criteria adopted GS, advances research, combined advocacy parent-based organisations, entry future

Language: Английский

Pharmacological Aspects in the Management of Children and Adolescents with Prader–Willi Syndrome DOI
Jennifer Miller,

Shivani Berry,

Esraa Ismail

et al.

Pediatric Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Language: Английский

Citations

0
Safety and efficacy of trofinetide in Rett syndrome: a systematic review and meta-analysis of randomized controlled trials DOI Creative Commons
Abdallah Abbas, Aya Mamdouh Fayoud,

Mostafa Hossam El Din Moawad

et al.

BMC Pediatrics, Journal Year: 2024, Volume and Issue: 24(1)

Published: March 23, 2024

Abstract Introduction Rett syndrome is a rare genetic neurodevelopmental disorder that predominantly impacts females. It presents with loss of acquired skills, impaired communication, and stereotypic hand movements. Given the limited treatment options for syndrome, there dire need effective interventions. Objective To evaluate safety efficacy trofinetide in Randomized Controlled Trials (RCTs) report on patients. Methods We identified 109 articles from four databases (Scopus, PubMed, Web Science, Cochrane CENTRAL). After removing duplicates, we narrowed them down to 59 further assessment. included RCTs evaluated patients syndrome. Three studies were eligible inclusion. Two independent reviewers studies’ titles, abstracts, full texts, extracting pertinent data. assessed quality using Risk Bias (RoB) 2.0 tool. then conducted meta-analysis fixed effects model case insignificant heterogeneity; otherwise, used random model. Based nature outcome, analyzed mean difference or odds ratio. Analysis was RevMan version 5.3. Results Among outcomes 181 group 134 placebo group, significant improvement Syndrome Behavior Questionnaire (RSBQ) scores observed at 200 mg dosage (overall difference: -3.53, p = 0.001). Clinical Global Impression-Improvement (CGI-I) improved considerably -0.34, < 0.0001). No substantial changes Motor Behavioral Assessment (MBA) Top 3 Caregiver Concerns. Treatment Emergent Adverse Events (TEAEs) across various dosages noted associations diarrhea (200 mg), vomiting irritability mg). However, did not find association between any incidence decreased appetite. Conclusion Trofinetide demonstrated potential improving RSBQ CGI-I dosage. Although no found MBA top caregiver concerns. events linked specific dosages.

Language: Английский

Citations

3
A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2023 DOI Creative Commons
Gizem Kaykı-Mutlu, Zinnet Şevval Aksoyalp,

Leszek Wojnowski

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: 397(5), P. 2949 - 2970

Published: March 26, 2024

Abstract With 54 new drugs and seven cellular gene therapy products, the approvals by US Food Drug Administration (FDA) recovered 2023 from 2022 dent back to levels of 2020–2021. As in previous years this annual review, we assign these one three innovation: first drug against a condition (“first-in-indication”), using novel molecular mechanism (“first-in-class”), “next-in-class,” i.e., an already exploited mechanism. We identify four (7%) “first-in-indication,” 22 (36%) “first-in-class,” 35 (57%) “next-in-class” drugs. By treatment area, rare diseases (54%) cancer (23%) were once again most prevalent (and partly overlapping) therapeutic areas. Other continuing trends use accelerated regulatory approval pathways reliance on biopharmaceuticals (biologics). marks based CRISPR/Cas9 editing.

Language: Английский

Citations

3
BIOCHEMICAL AND MOLECULAR DETERMINANTS OF THE SUBCLINICAL INFLAMMATORY MECHANISMS IN RETT SYNDROME DOI Creative Commons
Valeria Cordone

Archives of Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 757, P. 110046 - 110046

Published: May 28, 2024

To date, Rett syndrome (RTT), a genetic disorder mainly caused by mutations in the X-linked MECP2 gene, is increasingly considered broad-spectrum pathology, instead of just neurodevelopmental disease, due to multitude peripheral co-morbidities and compromised metabolic pathways, affecting patients. The altered molecular processes include an impaired mitochondrial function, perturbed redox homeostasis, chronic subclinical inflammation improper cholesterol metabolism. persistent inflammatory condition was first defined ten years ago, as previously unrecognized feature RTT, playing role pathology progress modulation phenotypical severity. In light this, present work aims at reviewing current knowledge on status immune/inflammatory functions well investigating emerging mechanisms underlying this with special focus latest findings about inflammasome system, autoimmunity responses intestinal micro- mycobiota. On these bases, although further research needed, future therapeutic strategies able re-establish adequate response could represent potential approaches for RTT

Language: Английский

Citations

3
A novel approach to metabolic profiling in case models of MECP2-related disorders DOI Creative Commons
Jessica A. Cooley Coleman, Bridgette A. Moffitt, William C. Bridges

et al.

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(2)

Published: Feb. 13, 2025

Abstract Genetic abnormalities of the MECP2 gene cause several conditions grouped under umbrella term -related disorders and characterized by a variety phenotypes. We applied functional approach to identify metabolic profiles in two patients with Rett syndrome (RTT) one patient duplication (MRXSL). Such an is based on Phenotype Mammalian Microarray (PM-M) technology, which designed assess cellular production energy presence different compounds generating distinct environments. The findings three case models were compared versus 50 controls. Although small number samples prevented most results from reaching significant p -values when adjusted Benjamini-Hochberg correction, some interesting trends emerged. Some indicated shared conditions, like increased sources such as pectin, adenosine, pyruvic acid, or decreased response certain hormones. Other showed opposite for disorders, interleukin-1 beta (IL-1 beta), caused RTT group but MRXSL. IL-1 also offers valuable insights into pathogenic mechanism potential therapeutic approaches. profiling bears remarkable translational since it may be helpful investigate molecular underlying phenotypical this spectrum develop biomarkers identification ideal candidates treatments recently approved trofenatide, targets development novel

Language: Английский

Citations

0
Trofinetide—a new chapter in rett syndrome’s treatment DOI Creative Commons
Muhammad Furqan

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 16, 2023

Trofinetide is the first drug approved by FDA to treat Rett Syndrome in children aged 2 years or above. The significantly improved syndrome behavioral scores questionnaire clinical studies. Although further research needed assess potential adverse events, Trofinetide's notable efficacy signifies a significant advancement treatment, offering new therapeutic avenue with ameliorate condition.

Language: Английский

Citations

6
Clinical Features and Disease Progression in Older Individuals with Rett Syndrome DOI Open Access
Jeffrey L. Neul, Tim A. Benke, Eric D. Marsh

et al.

Genes, Journal Year: 2024, Volume and Issue: 15(8), P. 1107 - 1107

Published: Aug. 22, 2024

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity would be associated genetic variants

Language: Английский

Citations

2
Deciphering the physiopathology of neurodevelopmental disorders using brain organoids DOI Creative Commons

Olivier Dionne,

Salomé Sabatié,

Benoît Laurent

et al.

Brain, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

Abstract Neurodevelopmental disorders (NDD) encompass a range of conditions marked by abnormal brain development in conjunction with impaired cognitive, emotional and behavioural functions. Transgenic animal models, mainly rodents, traditionally served as key tools for deciphering the molecular mechanisms driving NDD physiopathology significantly contributed to pharmacological interventions aimed at treating these disorders. However, efficacy treatments humans has proven be limited, due part intrinsic constraint models recapitulate complex structure human but also phenotypic heterogeneity found between affected individuals. Significant advancements field induced pluripotent stem cells (iPSCs) offer promising avenue overcoming challenges. Indeed, advanced differentiation protocols generating iPSC-derived organoids gives an unprecedented opportunity explore neurodevelopment. This review provides overview how 3D have been used investigate various (i.e. Fragile X syndrome, Rett Angelman microlissencephaly, Prader-Willi Timothy tuberous sclerosis syndrome) elucidate their pathophysiology. We discuss benefits limitations employing such innovative compared 2D cell culture systems realm personalized medicine.

Language: Английский

Citations

2
Profile of Trofinetide in the Treatment of Rett Syndrome: Design, Development and Potential Place in Therapy DOI Creative Commons
Laura Camillo, Marco Pozzi, Pia Bernardo

et al.

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 5023 - 5040

Published: Nov. 1, 2024

Trofinetide is a first-in-class pharmacological treatment proposed for patients with Rett Syndrome. It long half-life derivative of glycine-proline-glutamate, the tripeptide normally excided from Insulin-like Growth Factor 1 upon degradation. Due to containing glutamate and glycine in its structure, trofinetide thought act through NMDA receptor modulation, thus providing normalization neuronal activity survival. was tested series short long-term trials, showing good efficacy at improving scores on Clinical Global Impression-Improvement scale Syndrome Behavior Questionnaire, specific effect only some subscales, ie General Mood subscale Repetitive Face Movement subscale. No effects were documented other subscales or epilepsy, heart bone -related symptoms. The main adverse trofinetide, severe enough determine discontinuation, include diarrhea, vomiting, consequent weight loss. These may be scarcely avoidable, given need assume very large amount per day. Other inherent limitations use possibly regard limited duration drug supplies, as one bottle last three days only, depending weight, relatively high cost bottle. has no direct competitors: single symptoms Syndrome, instance, seizures aggressive behaviors, are currently treated drugs that have been developed without This leads suboptimal increased risk effects. place therapy yet determined, based results clinical practical usability, windows opportunity intervention. Moreover, curative if early during brain development, merely symptomatic young adults, data exist this aspect. will require reassessment after competing treatments enter market.

Language: Английский

Citations

1
Population Pharmacokinetics of Trofinetide in a Pediatric Population Aged 2–4 Years with Rett Syndrome DOI Creative Commons

Mona Darwish,

Julie Passarell,

Kelly Maxwell

et al.

Advances in Therapy, Journal Year: 2024, Volume and Issue: 42(2), P. 1009 - 1025

Published: Dec. 18, 2024

Language: Английский

Citations

1