Genetic Disease
Conditions
Keywords
leukodystrophy, antisense oligonucleotide, TUBB4A-related leukodystrophy, Hypomyelination, ASO
Brief summary
This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single pediatric participant with TUBB4A associated leukodystrophy.
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 pediatric participant with a de novo pathogenic gain of function TUBB4A mutation associated with severe leukodystrophy with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC)
Interventions
Drug: nL-TUBB4-001; Personalized antisense oligonucleotide
Sponsors
Massachusetts General Hospital
n-Lorem Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open label study
Intervention model description
Single participant interventional study
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
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. * Clinical phenotype and neuroimaging consistent with a diagnosis of TUBB4A-related leukodystrophy/Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-ABC) * Documented genetic mutation in TUBB4A
Exclusion criteria
* Participant has any known contraindication to or unwillingness to undergo lumbar puncture * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurological assessments | Baseline to 24 months | Change from baseline at 24 months post nL-TUBB4-001 administration in scores on the GMFM88, HINE-1, HINE-2, Bayley-4, and Vineland-3 developmental assessment scales, as well as the Tardieu Spasticity Scale and PedsQL Family Impact Module |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Feeding and swallow evaluation | Baseline to 24 months | Change from baseline at 24 months post nL-TUBB4-001 administration in assessment of feeding and swallow evaluation. |
| Safety and tolerability | Baseline to 24 months | Safety and tolerability |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORFlorian Eichler, MD
Massachusetts General Hospital
Outcome results
None listed