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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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)

Incidence and severity of treatment-emergent adverse events (AEs) from baseline to 12- and 24-months post nL-MAPK8-001 administration

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)

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)

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

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)

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)

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)

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.

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)

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)