Personalized Antisense Oligonucleotide for A Single Participant With GARS1 Gene Mutation Associated With Charcot-Marie-Tooth Disease Type 2D (CMT2D)

An Open-label Single Center, Single Participant Study of an Experimental Antisense Oligonucleotide Treatment for Charcot-Marie-Tooth Type 2D Due to GARS1 Genetic Mutation

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single participant with Charcot-Marie-Tooth disease type 2D (CMT2D) due to a pathogenic, de novo deletion mutation in GARS1

Study Overview

• Status: Enrolling by invitation
• Conditions: Charcot-Marie-Tooth Disease Type 2D
• Intervention / Treatment: Drug: nL-GARS1-001

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 CMT2D due to a pathogenic, de novo deletion mutation in GARS1

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

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • UTHealth Houston

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 the 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 GARS1 genetic variant

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-GARS1-001; Personalized antisense oligonucleotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor Skills	Change in fine motor skills from baseline to 12- and 24-months post nL-GARS1-001 administration as measured by the annualized rate of change in the Nine-Hole Peg Test (9-HPT)	Baseline to 24 months
Motor Skills	Change in fine motor skills from baseline to 12- and 24-months post nL-GARS1-001 administration as measured by the annualized rate of change in the Box and Block Test (BBT)	Baseline to 24 months
Motor Skills	Change in gross motor skills from baseline to 12- and 24-months post nL-GARS1-001 administration as measured by the annualized rate of change on Revised Upper Limb Module (RULM)	Baseline to 24 months
Motor Skills	Change in gross motor skills from baseline to 12- and 24-months post nL-GARS1-001 administration as measured by the annualized rate of change on Hammersmith Functional Motor Scale - Expanded (HFMSE)	Baseline to 24 months
Motor Skills	Change in gross motor skills from baseline to 12- and 24-months post nL-GARS1-001 administration as measured by the annualized rate of change on home videography assessment	Baseline to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life	Change in quality of life from baseline to 6-, 12-, 18- and 24-months post nL-GARS1-001 administration as measured by the Pediatric Quality of Life Inventory (PedsQL)	Baseline to 24 months
Functional Skills	Change in functional skills from baseline to 6-, 12-, 18- and 24-months post nL-GARS1-001 administration as measured by the Pediatric Evaluation of Disability Inventory - Computer Adaptive Test (PEDI-CAT)	Baseline to 24 months
Safety and Tolerability	Incidence and severity of treatment-emergent adverse events (AEs) post nL-GARS1-001 administration	Baseline to 24 months
Incidence of Treatment-Emergent Abnormalities in Physical Exam [Safety and Tolerability]	Changes post nL-GARS1-001 administration in physical examination (changes in appearance, skin, neck, ears, nose, throat, heart/lungs, abdomen, lymph nodes, and extremities compared to baseline)	Baseline to 24 months
Incidence of Treatment-Emergent Abnormalities in Neurological Exam [Safety and Tolerability]	Changes post nL-GARS1-001 administration in neurological examination (changes in mental status, gait, cerebellar, cranial nerve, motor, reflex, and sensations compared to baseline as assessed by treating physician)	Baseline to 24 months
Incidence of Treatment-Emergent Abnormalities in Safety Labs (CSF, chemistry, hematology, coagulation, and urinalysis) [Safety and Tolerability]	Emergent abnormalities in laboratory analyses (results outside of normal range for CSF, chemistry, hematology, coagulation, and urinalysis)	Baseline to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Function	Change in Forced Vital Capacity (FVC) from baseline to 12- and 24-months post nL-GARS1-001 administration	Baseline to 24 months
Pulmonary Function	Change in Forced Expiratory Volume in 1 second (FEV1) from baseline to 12- and 24-months post nL-GARS1-001 administration	Baseline to 24 months
Nerve Function	Change in nerve function from baseline to 12- and 24-months post nL-GARS1-001 administration as measured by speed and strength of electrical signals in the motor and sensory nerves	Baseline to 24 months
Cognition	Change in cognition from baseline to 12- and 24-months post nL-GARS1-001 administration as measured by NIH Toolbox Cognition assessment	Baseline to 24 months
Communication	Change in communication skills from baseline to 12- and 24-months post nL-GARS1-001 administration as measured by the Communication Participation Item Bank (CPIB)	Baseline to 24 months

Collaborators and Investigators

• Sponsor: n-Lorem Foundation
• Collaborators: The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: November 4, 2025
• First Submitted That Met QC Criteria: November 5, 2025
• First Posted (Actual): November 10, 2025

Study Record Updates

• Last Update Posted (Actual): November 10, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Charcot-Marie-Tooth disease, Type 2D
• Other Study ID Numbers: HSC-MS-25-0625

Drug and device information, study documents

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