ASO Treatment for Syndromic Craniosynostoses
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Design of patient specific ASO.
- Who it may be relevant to
- Registry conditions: Craniosynostoses, Crouzon Syndrome, Saethre Chotzen Syndrome, Muenke Syndrome. Basic parameters: up to 5 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Nano-ink Based Antisense oligonUcleoTIde deLivery for Ultra-personaIized Treatment of Syndromic Craniosynostoses
Overview
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.
Interventions
- Genetic 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
Primary outcome measures
- ASO design and development [Time frame: 12 months]
Secondary outcome measures (2)
- Nano-ink development [Time frame: 16 months]
- In vivo validation [Time frame: 16 months]
Eligibility criteria
Inclusion criteria
- 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.
Exclusion criteria
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
France · 1 center
- Institut Imagine — Paris
Identifiers
NCT: NCT07535372 · 26984