Personalized Antisense Oligonucleotide for A Single Participant (nL62541) With ATN1 Gene Mutation

An Open-label Single Center, Single Participant Study of an Experimental Antisense Oligonucleotide Treatment for Dentatorubral-pallidoluysian Atrophy (DRPLA) Due to ATN1 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-ATN1-001

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 DRPLA due to a heterozygous pathogenic CAG trinucleotide expansion in ATN1

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

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older 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
• 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-ATN1-001; 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) (changes in frequency of ictal and interictal discharges, evoked potentials, and changes in EEG background)	Baseline to 24 months
Seizures	Change in seizure length from baseline to every 3 months post nL-ATN1-002 administration as measured by seizure tracking (changes in number and length of seizures)	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)	Baseline to 24 months
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 Caregiver Global Impression of Change Questionnaire (CaGL-C)	Baseline to 24 months
Health Status	Change in comorbities 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)	Baseline to 24 months
Dysphagia	Change in swallow function and number of aspiration pneumonias (PNAs) from baseline to 12- and 24-months post nL-ATN1-002 administration as measured by Modified Barium Swallow Study (MBSS)	Baseline to 24 months
Dysphagia	Change in swallow function and number of aspiration pneumonias (PNAs) from baseline to 12- and 24-months post nL-ATN1-002 administration as measured by adverse events of aspiration PNAs	Baseline to 24 months
Incidence and Severity 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Developmental Skills	Change in developmental skills from baseline to 6-, 12-, 18-, and 24- months post nL-ATN1-002 administration as measured by Developmental Profile 4 (DP-4) (physical, adaptive behavior, social-emotional, cognitive, and communication scores)	Baseline to 24 months
Developmental Skills	Change in developmental skills from baseline to 6-, 12-, 18-, and 24- months post nL-ATN1-002 administration as measured by Bayley Scales of Infant Development 4 (BSID-4) (cognition, communication, motor, and adaptive behavior scores)	Baseline to 24 months
Developmental Skills	Change in developmental skills from baseline to 6-, 12-, 18-, and 24- months post nL-ATN1-002 administration as measured by Observer Reported Communication Ability (ORCA)	Baseline to 24 months
Ataxia	Change in ataxia from baseline to 6-, 12-, 18-, and 24- months post nL-ATN1-002 administration as measured by Scale for Assessment and Rating of Ataxia (SARA)	Baseline to 24 months
Brain Changes	Change in brain MRIs from baseline to 12- and 24- months post nL-ATN1-002 administration as measured by ventricular size on brain MRI	Baseline to 24 months

Collaborators and Investigators

• Sponsor: n-Lorem Foundation
• Collaborators: Dell Children's Medical Center of Central Texas

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: October 24, 2025
• First Submitted That Met QC Criteria: October 27, 2025
• First Posted (Actual): October 28, 2025

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: October 1, 2025

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: STUDY00007386

Drug and device information, study documents

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