Personalized Antisense Oligonucleotide Therapy for A Single Participant With ATN1 Gene Mutation

An Open-label Single Center, Single Participant Study of an Experimental Antisense Oligonucleotide Treatment for ATN1 Gene Mutation

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
  • New York
    • New York, New York, United States, 10027
      • Columbia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• 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.
• Genetically confirmed Dentatorubral-pallidoluysian atrophy (DRPLA) due to ATN1 mutation

Exclusion Criteria:

• Use of investigational medication within 5 half-lives of the drug at enrolment
• 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
Ataxia	Change in mobility and ataxia from baseline to 6-, 12-, 18- and 24-months post nL-ATN1-002 administration as measured by the Scale for Assessment and Rating of Ataxia (SARA).	Baseline to 24 months
Ataxia	Change in mobility and ataxia from baseline to 6-, 12-, 18- and 24-months post nL-ATN1-002 administration as measured by wrist/ankle accelerometers (peak velocity, peak acceleration, movement entropy).	Baseline to 24 months
Ataxia	Change in mobility and ataxia from baseline to 6-, 12-, 18- and 24-months post nL-ATN1-002 administration as measured by home gait video assessment (reviewed by blinded rater using gait and stance rating criteria from the SARA).	Baseline to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seizures	Change in seizure frequency and length of seizures, as well as seizure medication use, from baseline to 12- and 24-months post nL-ATN1-002 administration as measured by caregiver seizure diary tracking.	Baseline to 24 months
Quality of Life	Change in quality of life from baseline to 6-, 12-, 18- and 24-months post nL-ATN1-002 administration as measured by the Activities of Daily Living questionnaire (ADL).	Baseline to 24 months
Quality of Life	Change in quality of life from baseline to 6-, 12-, 18- and 24-months post nL-ATN1-002 administration as measured by the Caregiver Global Impression of Change questionnaire (CGI-C).	Baseline to 24 months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]		Baseline to 24 months
Incidence of Treatment-Emergent abnormalities in physical and neurological exams [Safety and tolerability]		Baseline to 24 months
Incidence of Treatment-Emergent abnormalities in safety labs (CSF, chemistry, hematology, coagulation, and urinalysis) [Safety and tolerability]		Baseline to 24 months

Collaborators and Investigators

• Sponsor: n-Lorem Foundation
• Collaborators: Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: November 21, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Actual): November 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Epileptic Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsies, Myoclonic; Epilepsy, Generalized; Epilepsy; Myoclonic Epilepsies, Progressive
• Other Study ID Numbers: AAAV0657

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No