Personalized Antisense Oligonucleotide for A Single Participant With PACS1 Gene Mutation Associated With Schuurs-Hoeijmakers Syndrome (SHMS)

An Open-label Single Center Study of an Experimental Antisense Oligonucleotide Treatment of a Participant With Schuurs-Hoeijmakers Syndrome Due to PACS1 Genetic Mutation

Status

Not yet recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07474298

Enrollment

Registered

2026-03-16

Start date

2026-04-01

Completion date

2028-04-01

Last updated

2026-03-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Schuurs-Hoeijmakers Syndrome

Brief summary

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug intended for a single participant with Schuurs-Hoeijmakers syndrome (SHMS) due to a pathogenic, de novo, heterozygous missense gain-of-function mutation in PACS1

Detailed description

This is an interventional study to evaluate the safety and efficacy of treatment with an individualized antisense oligonucleotide (ASO) treatment in a single participant with SHMS due to a pathogenic, de novo, heterozygous missense gain-of-function mutation in PACS1

Interventions

DRUGnL-PACS1-001

Personalized antisense oligonucleotide

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Healthy volunteers

Inclusion criteria

* Informed consent/assent provided by the participant's parent(s) or legally authorized representative(s) * Ability to travel to the study site and adhere to study-related follow-up examinations and/or procedures and provide access to participant's medical records * Genetically confirmed SHMS due to PACS1 gene mutationc.607C\>T (p.Arg203Trp)

Exclusion criteria

* Participant has any condition that in the opinion of the Site Investigator, would ultimately prevent the completion of study procedures * Participation in another investigational trial within 3 months of study enrollment or planned participation during the 24-month trial

Design outcomes

Primary

Measure	Time frame	Description
Communication Ability	Baseline to 24 months	Change in communication ability from baseline to 6-, 12-, 18-, and 24-months post nL-PACS1-001 administration as measured by Observer-Rated Communication Ability (ORCA) overall T-score

Secondary

Measure	Time frame	Description
Fine Motor Skills	Baseline to 24 months	Change in communication ability from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Vineland Adaptive Behavior Scales - Third Edition (Vineland-3) Fine Motor Subdomain Growth Scale Values (GSVs)
Safety and Tolerability	Baseline to 24 months	Incidence and severity of treatment-emergent adverse events (AEs) post nL-GPACS1-001 administration
Incidence of Treatment-Emergent Abnormalities in Physical Exam [Safety and Tolerability]	Baseline to 24 months	Changes post nL-PACS1-001 administration in physical examination (changes in appearance, skin, neck, ears, nose, throat, heart/lungs, abdomen, lymph nodes, and extremities compared to baseline)
Incidence of Treatment-Emergent Abnormalities in Neurological Exam [Safety and Tolerability]	Baseline to 24 months	Changes post nL-PACS1-001 administration in neurological examination (changes in mental status, gait, cerebellar, cranial nerve, motor, reflex, and sensations compared to baseline as assessed by treating physician)
Incidence of Treatment-Emergent Abnormalities in Safety Labs (CSF, chemistry, hematology, coagulation, and urinalysis) [Safety and Tolerability]	Baseline to 24 months	Emergent abnormalities in laboratory analyses (results outside of normal range for CSF, chemistry, hematology, coagulation, and urinalysis)

Countries

Canada

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 17, 2026