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

NCT07226297 | Enrolling By Invitation Phase 1 DMC FDA Drug

• 1 other identifier: HSC-MS-25-0625
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Charcot-Marie-Tooth Disease Type 2D

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (6)

• Quality of Life

  Baseline to 24 months

• Functional Skills

  Baseline to 24 months

• Safety and Tolerability

  Baseline to 24 months

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

  Baseline to 24 months

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

  Baseline to 24 months

Other Outcomes (5)

• Pulmonary Function

  Baseline to 24 months

• Pulmonary Function

  Baseline to 24 months

• Nerve Function

  Baseline to 24 months

Study Arms (1)

Open Label

EXPERIMENTAL

Drug: nL-GARS1-001

Interventions

nL-GARS1-001 DRUG

Personalized antisense oligonucleotide

Open Label

Eligibility Criteria

• Age: 13 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• n-Lorem Foundation: lead
• The University of Texas Health Science Center, Houston: collaborator

Study Sites (1)

UTHealth Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Charcot-Marie-Tooth disease, Type 2D

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2025
• First Posted: November 10, 2025
• Study Start: October 27, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: November 10, 2025

Record last verified: 2025-10

Locations

US (1)