The goal of this clinical trial is to learn if an antisense oligonucleotide (TS1-ASO) can safely treat and potentially prevent neuropsychiatric and neurodevelopmental symptoms in pediatric participants (age \>2 months) with Timothy Syndrome Type 1 (TS1).
The main questions it aims to answer are:
1. Is TS1-ASO safe and well tolerated when administered intrathecally in children with TS1? 2. What are the pharmacokinetics and preliminary efficacy of TS1-ASO on neurodevelopmental and neurologic outcomes?
This is a single-arm study (no comparison group).
Participants will:
1. Receive intrathecal injections of TS1-ASO via lumbar puncture using a stepwise dose-escalation approach 2. Undergo safety monitoring including neurologic exams, cardiac monitoring, laboratory testing, and adverse event assessments 3. Provide cerebrospinal fluid (CSF) and blood samples for pharmacokinetic and biomarker analyses 4. Complete neurodevelopmental, behavioral, and functional assessments (e.g., adaptive behavior, motor function, communication, seizure tracking) over time
Confirmed CACNA1C c.1216 G>A, p.G406R variant in exon 8A (TS1) on exome or genome testing.
Age > 2 months. Given that neurodevelopmental symptoms start early in TS1 and treatment is predicted to more effectively prevent rather than rescue developmental delay, ASD, and epilepsy, the Sponsor proposes that early treatment is most likely to yield clinical benefit.
Critical illness including cardiac arrhythmia that is unstable, invasive ventilatory support, sustained hypoglycemia, or active infection.
Diagnosis of a secondary genetic disorder in addition to TS1.
Hypoxic-ischemic injury to >25% of the brain from prior cardiac arrest.
Age > 5 years old with absence of any neurologic, developmental, or psychiatric diagnoses, or symptoms on physical exam and intake assessment scales as there would unlikely be a benefit to treatment in the setting of normal cognition and development and lack of epilepsy or other neuropsychiatric diagnoses.