Personalized Antisense Oligonucleotide for A Single Participant With ATN1 Gene Mutation

An Open-label, Single Center, Single Participant Study of an Experimental Antisense Oligonucleotide Treatment for ATN1 Mutation Associated Dentatorubral-pallidoluysian Atrophy (DRPLA)

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single participant with dentatorubral-pallidoluysian atrophy (DRPLA) due to a heterozygous pathogenic CAG trinucleotide expansion in ATN1

Study Overview

• Status: Active, not recruiting
• Conditions: Dentatorubral-Pallidoluysian Atrophy
• Intervention / Treatment: Drug: nL-ATN1-002

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 DRPLA due to a heterozygous pathogenic CAG trinucleotide expansion in ATN1

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

Contacts and Locations

Study Locations

• United States
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neuroscience

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Informed consent/assent provided by the participant (when appropriate), and/or 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.
• Clinical phenotype and neuroimaging consistent with a diagnosis of ATN1 mutation associated Dentatorubral-pallidoluysian atrophy (DRPLA).
• Documented genetic mutation in ATN1.

Exclusion Criteria:

• Participant has any known contraindication to or unwillingness to undergo lumbar puncture.
• Use of investigational medication within 5 half-lives of the drug at enrollment.
• Participant has any condition that in the opinion of the Site Investigator, would ultimately prevent the completion of study procedures.

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-ATN1-002; Personalized antisense oligonucleotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seizures	Change in seizure length from baseline to every 3 months post nL-ATN1-002 administration as measured by routine electroencephalography (EEG)	Baseline to 24 months
Seizures	Change in seizure frequency and seizure medication use from baseline to every 3 months post nL-ATN1-002 administration as measured by seizure tracking (reported with seizure dates and use of seizure medication).	Baseline to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life and Caregiver Burden	Change in quality of life and caregiver burden from baseline to 6-, 12-, 18-, and 24- months post nL-ATN1-002 administration as measured by the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD)	24 months
Health Status	Change in health issues from baseline to 6-, 12-, 18-, and 24-months post nL-ARN1-002 administration as measured by the Caregiver Priorities - Comorbidities and Health Evaluation Checklist (CPCHECKlist)	24 months
Incidence and Severity of Treatment Emergent Adverse Events [Safety and Tolerability]		24 months
Incidence of Treatment-Emergent Abnormalities in Physical and Neurological Exams [Safety and Tolerability]		24 months
Incidence of Treatment-Emergent Abnormalities in Safety Labs (CSF, chemistry, hematology, coagulation, and urinalysis) [Safety and Tolerability]		24 months

Collaborators and Investigators

• Sponsor: n-Lorem Foundation
• Collaborators: Hawaii Pacific Neuroscience

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: May 8, 2025
• First Submitted That Met QC Criteria: July 16, 2025
• First Posted (Actual): July 24, 2025

Study Record Updates

• Last Update Posted (Actual): July 24, 2025
• Last Update Submitted That Met QC Criteria: July 16, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Epileptic Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathological Conditions, Anatomical; Epilepsies, Myoclonic; Epilepsy, Generalized; Epilepsy; Atrophy; Myoclonic Epilepsies, Progressive
• Other Study ID Numbers: Pro00081366

Drug and device information, study documents

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