Personalized Antisense Oligonucleotide Therapy for a Participant With TARDBP ALS

An Open-label Study of an Experimental Antisense Oligonucleotide Treatment for Amyotrophic Lateral Sclerosis (ALS) Due to TARDBP (TDP-43) Genetic Mutation

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single participant with amyotrophic lateral sclerosis (ALS) due to a pathogenic variant in TARDBP.

Study Overview

• Status: Enrolling by invitation
• Conditions: Amyotrophic Lateral Sclerosis (ALS)
• Intervention / Treatment: Drug: nL-TARDB-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 amyotrophic lateral sclerosis (ALS) due to a pathogenic variant in TARDBP

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

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Informed consent/assent provided by the participant (when appropriate), and/or participants 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 neurological disorder

Exclusion Criteria:

• Participant has any condition that in the opinion of the Site Investigator, would ultimately prevent the completion of study procedures
• Use of an investigational medication within less than 5 half-lives of the drug at enrollment

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-TARDB-002; Personalized antisense oligonucleotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Functioning	Change from baseline at 12-months post nL-TARDB-002 administration in scores on Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R).	Baseline to 12 months
Clinical Functioning	Change from baseline at 12-months post nL-TARDB-002 administration in Slow Vital Capacity (SVC)	Baseline to 12 months
Clinical Functioning	Change from baseline at 12-months post nL-TARDB-002 administration in Handheld Dynamometry (HHD)	Baseline to 12 months
Clinical Functioning	Change from baseline at 12-months post nL-TARDB-002 administration in scores on Edinburgh Cognitive and Behavioral ALS Screen (ECAS).	Baseline to 12 months
Clinical Functioning	Change from baseline at 12-months post nL-TARDB-002 administration in scores on ALS Cognitive Behavioral Screen (ALS-CBS).	Baseline to 12 months
Clinical Functioning	Change from baseline at 12-months post nL-TARDB-002 administration in scores on Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5).	Baseline to 12 months
Survival	Change from baseline at 12-months post nL-TARDB-002 administration in survival status	Baseline to 12 months
Disease Biomarkers	Change from baseline at 12-months post nL-TARDB-002 administration in serum/plasma and CSF neurofilament light chain levels	Baseline to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	Emergent abnormalities in physical exam	Baseline to 12 months
Safety and Tolerability	Incidence and severity of adverse events	Baseline to 12 months
Safety and Tolerability	Emergent abnormalities in neurological exam	Baseline to 12 months
Safety and Tolerability	Emergent abnormalities in safety labs (CSF, chemistry, hematology, coagulation, and urinalysis)	Baseline to 12 months
Safety and Tolerability	Emergent abnormalities in electrocardiogram (ECG)	Baseline to 12 months

Collaborators and Investigators

• Sponsor: n-Lorem Foundation
• Collaborators: Thomas Jefferson University

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 9, 2026
• First Submitted That Met QC Criteria: July 9, 2026
• First Posted (Actual): July 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: NLF-TARDB-002-A

Drug and device information, study documents

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