Personalized Antisense Oligonucleotide for a Single Participant With MAPK8IP3 Neurodevelopmental Disorder With or Without Variable Brain Abnormalities (NEDBA)

An Open-label Single Center, Single Participant Study of an Experimental Antisense Oligonucleotide Treatment for Neurodevelopmental Disorder With or Without Variable Brain Abnormalities (NEDBA) Due to MAPK8IP3 Mutation

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single participant with Neurodevelopmental Disorder with or without Brain Abnormalities (NEDBA) due to a heterozygous pathogenic missense mutation in MAPK8IP3

Study Overview

• Status: Active, not recruiting
• Conditions: Neurodevelopmental Disorder With or Without Variable Brain Abnormalities
• Intervention / Treatment: Drug: nL-MAPK8-001

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 NEDBA due to a heterozygous pathogenic missense mutation in MAPK8IP3

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

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Informed consent/assent provided by the participant (when appropriate), and/or 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 neurodevelopmental disorder due to MAPK8IP3 mutation

Exclusion Criteria:

• Use of investigational medication within 5 half-lives of the drug at enrolment
• 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-MAPK8-001; Personalized antisense oligonucleotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor Skills	Change in gross motor function from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by the Gross Motor Function Measure-88 score.	Baseline to 24 months
Motor Skills	Change in gross motor function from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by the Gross Motor Function Classification Scale (GMFCS) score.	Baseline to 24 months
Motor Skills	Change in gross motor function from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by the Manual Ability Classification Scale (MACS) level.	Baseline to 24 months
Motor Skills	Change in gross motor function from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by the Bayley Scales of Infant and Toddler Development 4th Edition (BSID-4) score.	Baseline to 24 months
Motor Skills	Change in gross motor function from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by the Vineland Adaptive Behavior Scales - Third Edition (Vineland-3) score.	Baseline to 24 months
Motor Skills	Change in gross motor function from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by distance, velocity, acceleration, movement shape, and entropy of movement captured on wrist and ankle accelerometers.	Baseline to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seizure Onset	Change in presence of seizures from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by number of seizures recorded by EEG monitoring.	Baseline to 24 months
Seizure Onset	Change in presence of seizures from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by changes in caregiver reported seizure tracker.	Baseline to 24 months
Respiratory Infections	Change in frequency of treatment and hospitalizations for respiratory infection from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by changes in concomitant medications.	Baseline to 24 months
Respiratory Infections	Change in frequency of treatment and hospitalizations for respiratory infection from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by frequence of adverse events.	Baseline to 24 months
Sleep Quality	Change in sleep architecture from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured using an actigraphy device to monitor sleep duration.	Baseline to 24 months
Quality of Life	Change in quality of life from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by Caregiver Global Impression of Change questionnaire (CaGI-C)	Baseline to 24 months
Safety and Tolerability	Incidence and severity of treatment-emergent adverse events (AEs) from baseline to 12- and 24-months post nL-MAPK8-001 administration	Baseline to 24 months
Safety and Tolerability	Changes from baseline to 12- and 24-months post nL-MAPK8-001 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 from baseline to 12- and 24-months post nL-MAPK8-001 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, 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
Communication	Change in communication skills from baseline to 6-, 12-, 18-, and 24-months post nL-MAPK8-002 administration as measured by Observer-Reported Communication Ability (ORCA)	Baseline to 24 months
Communication	Change in communication skills from baseline to 12-, and 24-months post nL-MAPK8-002 administration as measured by Bayley Scales of Infant and Toddler Development 4th Edition (BSID-4)	Baseline to 24 months
Communication	Change in communication skills from baseline to 12-, and 24-months post nL-MAPK8-002 administration as measured by Vineland Adaptive Behavior Scales - third Edition (Vineland-3)	Baseline to 24 months
Swallow function	Change in swallow function from baseline to 12-, and 24-months post nL-MAPK8-002 administration as measured by a formal swallow study changes in oral and pharyngeal phases.	Baseline to 24 months
Swallow Function	Change in swallow function from baseline to 12-, and 24-months post nL-MAPK8-002 administration as measured by Pediatric Functional Oral Intake Scale (pFOIS)	Baseline to 24 months
Swallow Function	Change in swallow function from baseline to 12-, and 24-months post nL-MAPK8-002 administration as measured by Eating and Drinking Ability Classification System for individuals with CP (EDACS)	Baseline to 24 months

Collaborators and Investigators

• Sponsor: n-Lorem Foundation
• Collaborators: Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: July 23, 2025
• First Submitted That Met QC Criteria: September 22, 2025
• First Posted (Estimated): September 29, 2025

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: AAAV6360

Drug and device information, study documents

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