CraniosynostosesNAUTILUSNCT07535372
ASO Treatment for Syndromic Craniosynostoses
An observational study of Craniosynostoses and Crouzon Syndrome, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
Syndromic craniosynostoses (SCS) are rare genetic disorders defined by premature cranial suture fusion, resulting in abnormal craniofacial development and constrained brain growth. Read more about this study
- Who is it for?
- Ages Up to 5 years
- Conditions the study is for
- Craniosynostoses, Crouzon Syndrome, Saethre Chotzen Syndrome
- What is being tested?
- Design of patient specific ASO
- How many people
- 12 participants
- Where
- 1 siteItaly
- Study dates
- 20 Apr 2026to 20 Apr 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 5 years
- All sexes
- No healthy volunteers
- Child
Study population: Prospective and retrospective paediatric patients, undergoing/underwent corrective surgery for craniosynostosis as per standard of care, will be enrolled at Policlinico Gemelli upon obtain a written informed consent by their parents/legal guardians. Patient selection will be based on genetic evaluations from prior testing conducted as part of their clinical management. A total of 12 patients, with confirmed genetic diagnosis of SCS, with at least 4 different disease-causing mutations, will be selected for the study and cells isolated from their suture samples (surgical waste) analysed.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Cellular and Experimental Biology Unit
Rome, 00168
Wanda Lattanzi, MD, PhD, +390630156946, wanda.lattanzi@unicatt.it
Wanda Lattanzi, MD, PhD
About this study
Official title: Nano-ink Based Antisense oligonUcleoTIde deLivery for Ultra-personaIized Treatment of Syndromic Craniosynostoses
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.
Read more
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.
- Conditions
- Craniosynostoses, Crouzon Syndrome, Saethre Chotzen Syndrome, Muenke Syndrome, Pfeiffer Syndrome, Apert Syndrome
- Being tested
- Design of patient specific ASO
- Medical subject headings
- Craniosynostoses, Craniofacial Dysostosis, Acrocephalosyndactylia, Muenke Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Design of patient specific ASOGenetic
For each patient enrolled cranial suture tissue waste and peripheral blood sample will be collected for cell isolation and ASO in vitro testing
What is being measured
The primary outcome is the main question the study is designed to answer.
ASO design and development
Development of personalized therapeutic ASOs to restore the expression/function of disease-causing genes in patient-derived suture cells.
Measured: 12 months
Secondary outcomes (2)
Nano-ink development
Formulation of hydrogel-based nano-ink embedded with functionalized PLGA-PEG-bis-sulfone (PPB) NPs able to deliver and release of therapeutic ASOs.
Measured: 16 months
In vivo validation
Validation of ASO efficiency in murine model tissue
Measured: 16 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2026
- Study start20 Apr 2026
- Primary completion20 Apr 2027 (estimated)
- Study completion20 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CraniosynostosesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wanda Lattanzi, Principal investigator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07535372
- Sponsor's protocol ID
- 26984
- Other IDs
- ID: 29548
- Acronym
- NAUTILUS
- Status last verified
- Apr 2026
- First submitted
- 10 Apr 2026
- Last updated
- 8 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nano-ink Based Antisense oligonUcleoTIde deLivery for Ultra-personaIized Treatment of Syndromic Craniosynostoses
- ClinicalTrials.gov ID
- NCT07535372
- Acronym / sponsor ID
- NAUTILUS / 26984
- Conditions
- Craniosynostoses, Crouzon Syndrome, Saethre Chotzen Syndrome, Muenke Syndrome, Pfeiffer Syndrome, Apert Syndrome
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 20 Apr 2026 (actual)
- Primary completion
- 20 Apr 2027 (estimated)
- Study completion
- 20 Apr 2028 (estimated)
- First posted
- 17 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- Up to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Prospective and retrospective paediatric patients, undergoing/underwent corrective surgery for craniosynostosis as per standard of care, will be enrolled at Policlinico Gemelli upon obtain a written informed consent by their parents/legal guardians. Patient selection will be based on genetic evaluations from prior testing conducted as part of their clinical management. A total of 12 patients, with confirmed genetic diagnosis of SCS, with at least 4 different disease-causing mutations, will be selected for the study and cells isolated from their suture samples (surgical waste) analysed.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Design of patient specific ASOFor each patient enrolled cranial suture tissue waste and peripheral blood sample will be collected for cell isolation and ASO in vitro testing | Genetic | – |
Primary outcome
ASO design and development
Time frame: 12 months
Development of personalized therapeutic ASOs to restore the expression/function of disease-causing genes in patient-derived suture cells.
2 secondary outcomes
Nano-ink development
Time frame: 16 months
In vivo validation
Time frame: 16 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Wanda Lattanzi principal investigator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Craniosynostoses and Crouzon Syndrome, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wanda Lattanzi, MD, PhD (+390630156946, wanda.lattanzi@unicatt.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ASO design and development (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2026.