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Enrolling by Invitation

NCT Number: NCT07226297

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

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

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Key information

Conditions

Charcot-Marie-Tooth Disease Type 2D Charcot-Marie-Tooth disease, Type 2D

Age range

13 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

UTHealth Houston

Houston, Texas, 77030, United States

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

nL-GARS1-001

Drug

Personalized antisense oligonucleotide

Primary outcomes

  1. Motor Skills

    Time frame: Baseline to 24 months

    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)

  2. Motor Skills

    Time frame: Baseline to 24 months

    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)

  3. Motor Skills

    Time frame: Baseline to 24 months

    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)

  4. Motor Skills

    Time frame: Baseline to 24 months

    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)

  5. Motor Skills

    Time frame: Baseline to 24 months

    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

Secondary outcomes

  1. Quality of Life

    Time frame: Baseline to 24 months

    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)

  2. Functional Skills

    Time frame: Baseline to 24 months

    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)

  3. Safety and Tolerability

    Time frame: Baseline to 24 months

    Incidence and severity of treatment-emergent adverse events (AEs) post nL-GARS1-001 administration

  4. Incidence of Treatment-Emergent Abnormalities in Physical Exam [Safety and Tolerability]

    Time frame: Baseline to 24 months

    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)

  5. Incidence of Treatment-Emergent Abnormalities in Neurological Exam [Safety and Tolerability]

    Time frame: Baseline to 24 months

    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)

  6. Incidence of Treatment-Emergent Abnormalities in Safety Labs (CSF, chemistry, hematology, coagulation, and urinalysis) [Safety and Tolerability]

    Time frame: Baseline to 24 months

    Emergent abnormalities in laboratory analyses (results outside of normal range for CSF, chemistry, hematology, coagulation, and urinalysis)

Other outcomes

  1. Pulmonary Function

    Time frame: Baseline to 24 months

    Change in Forced Vital Capacity (FVC) from baseline to 12- and 24-months post nL-GARS1-001 administration

  2. Pulmonary Function

    Time frame: Baseline to 24 months

    Change in Forced Expiratory Volume in 1 second (FEV1) from baseline to 12- and 24-months post nL-GARS1-001 administration

  3. Nerve Function

    Time frame: Baseline to 24 months

    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

  4. Cognition

    Time frame: Baseline to 24 months

    Change in cognition from baseline to 12- and 24-months post nL-GARS1-001 administration as measured by NIH Toolbox Cognition assessment

  5. Communication

    Time frame: Baseline to 24 months

    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)

Sponsors and collaborators

Lead sponsor

n-Lorem Foundation

Other

Collaborators

  • The University of Texas Health Science Center, Houston

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Nov 10, 2025
Registry last updated
Nov 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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