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Набор скоро начнётся NCT07535372

ASO Treatment for Syndromic Craniosynostoses

— Наблюдательное Craniosynostoses Crouzon Syndrome Saethre Chotzen Syndrome Muenke Syndrome

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают
В протоколе указаны: Design of patient specific ASO.
Кому может быть актуально
Состояния в реестре: Craniosynostoses, Crouzon Syndrome, Saethre Chotzen Syndrome, Muenke Syndrome. Базовые параметры: до 5 лет · Все.
Что важно проверить
Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится
Франция
Следующий шаг
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Официальное название

Nano-ink Based Antisense oligonUcleoTIde deLivery for Ultra-personaIized Treatment of Syndromic Craniosynostoses

Обзор

Syndromic craniosynostoses (SCS) are rare genetic disorders defined by premature cranial suture fusion, resulting in abnormal craniofacial development and constrained brain growth. These conditions, including Muenke, Saethre-Chotzen, Crouzon, Apert, Pfeiffer and craniofrontonasal syndromes, are typically caused by gain- or loss-of-function variants in key regulators of suture biology such as FGFR1/2/3, TWIST1 and TCF12. Current management is exclusively surgical, relying on early cranial vault remodelling and subsequent reconstructive procedures, which carry substantial risks (e.g. blood loss, infection, re-synostosis) and do not address the underlying molecular etiology. Recent advances in RNA-based therapeutics have demonstrated the potential of mutation-specific approaches to normalize aberrant osteogenic differentiation in patient-derived cells. However, clinical translation remains limited by inefficient delivery and lack of sustained therapeutic activity. The NAUTILUS project aims to overcome these barriers by developing a non-invasive, ultra-personalized therapeutic platform based on mutation-specific antisense oligonucleotides (ASOs) delivered via a nano-engineered system. The project will design and validate patient-tailored ASOs targeting the molecular drivers of SCS, with the goal of either silencing pathogenic gain-of-function alleles or restoring physiological expression in loss-of-function contexts. Functional efficacy will be assessed in patient-derived cellular models by evaluating transcript modulation and rescue of protein function. In parallel, NAUTILUS will optimize a nano-ink delivery platform combining PLGA-PEG-bis-sulfone nanoparticles with a GelMA-based hydrogel scaffold, enabling localized, controlled, and sustained ASO release within the cranial suture niche. Preclinical validation in relevant mouse models will assess the capacity of this platform to delay or prevent pathological suture ossification, ultimately reducing the need for repeated surgical interventions. By directly targeting the genetic basis of disease, NAUTILUS proposes a transformative approach to SCS management. This strategy has the potential to decrease treatment invasiveness, improve clinical outcomes, and enhance quality of life, establishing a precision medicine paradigm for rare craniofacial disorders.

Вмешательства

  • Генная терапия Design of patient specific ASO
    For each patient enrolled cranial suture tissue waste and peripheral blood sample will be collected for cell isolation and ASO in vitro testing

Первичные конечные точки

  • ASO design and development [Срок оценки: 12 months]
Вторичные конечные точки (2)
  • Nano-ink development [Срок оценки: 16 months]
  • In vivo validation [Срок оценки: 16 months]

Критерии участия

Критерии включения

  • Paediatric patients (0-5 years), with a confirmed genetic diagnosis of syndromic craniosynostosis involving pathogenic GoF or LoF variants in FGFR1-3, TWIST1, TCF12, EFNB1, ERF, MSX2, or ALX4.
  • Availability of cranial-suture tissue fragments obtained during surgical remodelling procedures and classified as surgical waste.
  • Signed informed consent from parents or legal guardians.

Критерии исключения

  • Patients older than 5 years.
  • Patients aged 0-5 years with conditions unrelated to syndromic craniosynostosis in the selected genes.
  • Genetic variants of uncertain significance or undetermined molecular diagnosis.
  • Tissue samples with insufficient quantity or inadequate quality for cell isolation or culture.
  • Refusal of informed consent.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения
Когортное

Центры проведения

Франция · 1 центр
  • Institut Imagine — Paris

Идентификаторы

NCT: NCT07535372 · 26984

Первоисточники (государственные реестры)

Открыть это исследование на ClinicalTrials.gov ↗