Personalized Antisense Oligonucleotide Therapy for A Single Participant With LMNB1 Mutation Associated Autosomal Dominant Leukodystrophy (ADLD)

Phase 1

Active, not recruiting

• Conditions: Autosomal Dominant Leukodystrophy
• Interventions: Drug: nL-LMNB1-001

• Registration Number: NCT06816498
• Lead Sponsor: n-Lorem Foundation

Brief Summary

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single participant with Autosomal Dominant Leukodystrophy (ADLD) due to LMNB1 mutation

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 Autosomal Dominant Leukodystrophy (ADLD) due to LMNB1 mutation

Study Timeline

• Study First Submitted: 2025-01-28
• Study First Submitted QC: 2025-02-03
• Study First Posted: 2025-02-10
• Study Start: 2025-03-17
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-30
• Last Update Posted: 2025-05-04
• Primary Completion: 2027-03
• Study Completion: 2027-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 1

Inclusion Criteria

• Informed consent provided by the participant (when appropriate), and/or participant's parent(s) or legally authorized representative(s).
• Autosomal dominant adult-onset leukodystrophy (ADLD) caused by an LMNB1 duplication mutation
• 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.
• Willingness to follow contraceptive guidance during the intervention period and for at least 40 weeks after the last dose of study intervention

Exclusion Criteria

• Participant has any condition that in the opinion of the Site Investigator, would ultimately prevent the completion of study procedures

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open Label	nL-LMNB1-001	-

Primary Outcome Measures

Name	Time	Method
Gait	Baseline to 24 months	Change in gait from baseline at 6-, 12-, 18- and 24-months post nL-LMNB1-001 administration as measured by 25-feet walk test
Neurological functioning	Baseline to 24 months	Change in neurological functioning results from baseline at 6-, 12-, 18- and 24-months post nL-LMNB1-001 administration as measured by formal neuro-psychological evaluation (abnormalities in cognitive functioning such as memory, visual function, and language function).
Brain atrophy	Baseline to 24 months	Change in degree of brain atrophy from baseline at 6-, 12-, 18- and 24-months post nL-LMNB1-001 administration as measured by brain MRI

Secondary Outcome Measures

Name	Time	Method
Autonomic function	Baseline to 24 months	Change from baseline at 6-, 12-, 18- and 24-months post nL-LMNB1-001 administration in autonomic function as measured by 24-hour ambulatory blood pressure monitoring
Incidence of Treatment-Emergent abnormalities in physical and neurological exams [Safety and Tolerability]	Baseline to 24 months
Urodynamics	Baseline to 24 months	Change from baseline at 6-, 12-, 18- and 24-months post nL-LMNB1-001 administration in urodynamic study (normal or abnormal bladder activity).
Incidence of Treatment-Emergent abnormalities in safety labs (CSF, chemistry, hematology, coagulation, and urinalysis) [Safety and Tolerability]	Baseline to 24 months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Baseline to 24 months

Trial Locations

Locations (1)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States