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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Schuurs-Hoeijmakers Syndrome
• Intervention / Treatment: Drug: nL-PACS1-001

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

• Study Type: Interventional
• Enrollment (Estimated): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children (SickKids)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open Label	Drug: nL-PACS1-001; Personalized antisense oligonucleotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Communication Ability	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	Baseline to 24 months
Communication Ability	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) growth scale values (GSVs) for Expressive Language and Receptive Language subdomains	Baseline to 24 months
Communication Ability	Change in communication ability from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Bayley Scales of Infant and Toddler Development 4th Edition (BSID-4) Expressive and Receptive Language domains	Baseline to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Abnormalities in Safety Labs (CSF, chemistry, hematology, coagulation, and urinalysis) [Safety and Tolerability]	Emergent abnormalities in laboratory analyses (results outside of normal range for CSF, chemistry, hematology, coagulation, and urinalysis)	Baseline to 24 months
Fine Motor Skills	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)	Baseline to 24 months
Fine Motor Skills	Change in fine motor skills from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Bayley Scales of Infant and Toddler Development 4th Edition (BSID-4) Fine motor domain	Baseline to 24 months
Fine Motor Skills	Change in fine motor skills from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Hammersmith Infant Neurological Examination (HINE) overall score	Baseline to 24 months
Fine Motor Skills	Change in fine motor skills every 28 days for 24-months post nL-PACS1-001 administration as measured by Early Motor Questionnaire (EMQ)	Baseline to 24 months
Safety and Tolerability	Incidence and severity of treatment-emergent adverse events (AEs) post nL-GPACS1-001 administration	Baseline to 24 months
Incidence of Treatment-Emergent Abnormalities in Physical Exam [Safety and Tolerability]	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)	Baseline to 24 months
Incidence of Treatment-Emergent Abnormalities in Neurological Exam [Safety and Tolerability]	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)	Baseline to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognition and Behavior and Socialization	Change in cognition, behavior, and socialization from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Repetitive Behavior Scale - Revised (RBS-R)	Baseline to 24 months
Cognition and Behavior and Socialization	Change in cognition, behavior, and socialization 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), Daily Living and Socialization Domain GSVs for Community, Domestic and Personal Subdomains and Coping Skills, Play and Leisure and Interpersonal Relationships Subdomains	Baseline to 24 months
Cognition and Behavior and Socialization	Change in cognition, behavior, and socialization from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Bayley Scales of Infant and Toddler Development 4th Edition (BSID-4) Cognition Domain	Baseline to 24 months
Seizures	Change in frequency of clinical seizures from baseline to 6-, 12-, 18-, and 24-months post nL-PACS1-001 administration as measured by spike counts during sleep per unit time during 24-hour overnight clinical Electroencephalography (EEG)	Baseline to 24 months
Seizures	Change in frequency of clinical seizures from baseline to 6-, 12-, 18-, and 24-months post nL-PACS1-001 administration as measured by seizure diary	Baseline to 24 months
Sleep and Drooling	Change in sleep and drooling every 28 days from baseline to 24-months post nL-PACS1-001 administration as measured by Measure Your Own Medical Profile-2 (MYOMP-2) targets of drooling and sleep	Baseline to 24 months
Sleep and Drooling	Change in sleep and drooling from baseline to 12- and 24-months post nL-PACS1-001 administration as measured by Brief Infant Sleep Questionnaire (BISQ)	Baseline to 24 months
Cerebrospinal Fluid (CSF) Composition	Change in composition of CSF from baseline to 6-, 12-, 18-, and 24- months post nL-PACS1-001 administration as assessed by cerebrospinal fluid analysis	Baseline to 24 months

Collaborators and Investigators

• Sponsor: n-Lorem Foundation
• Collaborators: The Hospital for Sick Children (SickKids)

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 11, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: NLF-HC-0001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No