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

An Open-label, Single-center, Single-participant Study of an Experimental Antisense Oligonucleotide Treatment for a Patient With LMNB1 Mutation Associated Autosomal Dominant Leukodystrophy (ADLD)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Autosomal Dominant Leukodystrophy
• Intervention / Treatment: Drug: nL-LMNB1-001

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 Autosomal Dominant Leukodystrophy (ADLD) due to LMNB1 mutation

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

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

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

Description

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 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-LMNB1-001; Personalized antisense oligonucleotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gait	Change in gait from baseline at 6-, 12-, 18- and 24-months post nL-LMNB1-001 administration as measured by gait motion analysis	Baseline to 24 months
Gait	Change in gait from baseline at 6-, 12-, 18- and 24-months post nL-LMNB1-001 administration as measured by 6-minute walk test	Baseline to 24 months
Gait	Change in gait from baseline at 6-, 12-, 18- and 24-months post nL-LMNB1-001 administration as measured by 25-feet walk test	Baseline to 24 months
Neurological functioning	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).	Baseline to 24 months
Brain atrophy	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	Baseline to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]		Baseline to 24 months
Urodynamics	Change from baseline at 6-, 12-, 18- and 24-months post nL-LMNB1-001 administration in urodynamic study (normal or abnormal bladder activity).	Baseline to 24 months
Autonomic function	Change from baseline at 6-, 12-, 18- and 24-months post nL-LMNB1-001 administration in autonomic function as measured by % anhidrosis from thermoregulatory sweat test	Baseline to 24 months
Autonomic function	Change from baseline at 6-, 12-, 18- and 24-months post nL-LMNB1-001 administration in autonomic function as measured by Quantitative Axon Reflex Sweat Test sweat output (uL)	Baseline to 24 months
Autonomic function	Change from baseline at 6-, 12-, 18- and 24-months post nL-LMNB1-001 administration in autonomic function as measured by supine and standing catecholamines levels	Baseline to 24 months
Autonomic function	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	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: Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: January 28, 2025
• First Submitted That Met QC Criteria: February 3, 2025
• First Posted (Actual): February 10, 2025

Study Record Updates

• Last Update Posted (Actual): May 4, 2025
• Last Update Submitted That Met QC Criteria: April 30, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Joint Diseases; Musculoskeletal Abnormalities; Congenital Abnormalities; Arthrogryposis
• Other Study ID Numbers: 23-011942

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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