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
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
1
Personalized antisense oligonucleotide
The Hospital for Sick Children (SickKids)
Toronto, Ontario, Canada
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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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
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Time frame: 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)
Time frame: Baseline to 24 months
Safety and Tolerability
Incidence and severity of treatment-emergent adverse events (AEs) post nL-GPACS1-001 administration
Time frame: 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)
Time frame: 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)
Time frame: Baseline to 24 months
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)
Time frame: Baseline to 24 months