Antisense Oligonucleotide Treatment for Leukodystrophy

(ASOTUBB4A Trial)

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, San Diego

Must not be taking: Investigational drugs

Disqualifiers: Lumbar puncture contraindication, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called nL-TUBB4-001 (an antisense oligonucleotide) for individuals with TUBB4A-related leukodystrophy, a rare brain disorder. The goal is to determine if this treatment can help manage the condition in those with a specific genetic mutation and matching symptoms. Participants must be able to travel to the study site and have a TUBB4A genetic mutation confirmed by their doctor. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use investigational medications close to the start of the trial. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Previous studies have examined the safety of nL-TUBB4-001, a new treatment for leukodystrophy. Researchers have focused on how well participants tolerate the treatment over time. They monitored participants for changes in their ability to eat and swallow, key indicators of safety. Reports have concentrated on these abilities to ensure the treatment does not cause harm.

This study is in the early stages, so safety is still under careful scrutiny. Early studies like this primarily aim to determine if the treatment is safe enough for further testing. Although final data is not yet available, the ongoing study suggests some confidence in its initial safety. However, as with any new treatment, unknown risks may exist. Researchers closely monitor participants to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about nL-TUBB4-001 for leukodystrophy because it uses antisense oligonucleotides, which is a novel approach compared to the standard treatments that mainly involve symptom management and supportive care. This treatment specifically targets the genetic mutations causing the disorder, offering a more precise and potentially transformative therapy. Unlike traditional therapies, nL-TUBB4-001 aims to alter the disease's progression at a molecular level, which could lead to significant improvements in patient outcomes and quality of life.

What evidence suggests that this treatment might be an effective treatment for leukodystrophy?

Research has shown that a treatment called antisense oligonucleotide (ASO), specifically nL-TUBB4-001, could be promising for conditions like TUBB4A-related leukodystrophy. This treatment targets and corrects specific genetic mutations causing the disease. Earlier studies have demonstrated that ASOs can improve symptoms by directly addressing these genetic issues. For TUBB4A-related leukodystrophy, early animal studies suggested that ASO can help restore certain brain functions affected by the disease. Although limited data exists from human studies, the personalized approach of ASO treatment offers hope for effectively managing this condition. Participants in this trial will receive the ASO treatment in an open-label format. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for a single participant with TUBB4A-related leukodystrophy, who can travel to the study site and follow the procedures. They must have a confirmed genetic mutation in TUBB4A and show typical symptoms and brain imaging results. People using other investigational drugs or unable to complete the study are excluded.

Inclusion Criteria

Informed consent/assent provided by the participant (when appropriate), and/or participant's parent(s) or legally authorized representative(s)

I can travel to the study location and follow the study's schedule.

My diagnosis is TUBB4A-related leukodystrophy, confirmed by clinical and MRI findings.

Exclusion Criteria

Use of investigational medication within 5 half-lives of the drug at enrollment

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

I cannot or do not want to have a lumbar puncture.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an experimental antisense oligonucleotide treatment for TUBB4A-related leukodystrophy

24 months

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• nL-TUBB4-001

Trial Overview

The trial tests an experimental antisense oligonucleotide treatment called nL-TUBB4-001 on one person with TUBB4A-related leukodystrophy, focusing on its potential effects on this specific genetic disorder that affects myelination in the brain.

How Is the Trial Designed?

Group I: Open label Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07222371

Study Details | NCT07222371 | An Open-label, Single ...

The study is an investigational interventional drug created for the study subject's specific pathogenic genetic mutation. Official Title. An Open-label, Single ...

2.

trial.medpath.com

trial.medpath.com/clinical-trial/60ebf6b81ac569d0/nct06369974-experimental-antisense-oligonucleotide-treatment-tubb4a-leukodystrophy

Single Participant Study of an Experimental ASO Treatment for ...

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single pediatric participant with TUBB4A associated ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06369974

Single Participant Study of an Experimental ASO Treatment ...

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single pediatric participant with TUBB4A ...

4.

biorxiv.org

biorxiv.org/content/10.1101/2024.08.27.609903v2.full.pdf

Therapeutic suppression of Tubb4a rescues H-ABC ...

517. H-ABC leukodystrophy involves cell-autonomous deficits in OLs, CGNs, and striatal. 518 neurons, making it difficult to develop a treatment ...

5.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK395611/

TUBB4A-Related Leukodystrophy - GeneReviews - NCBI - NIH

TUBB4A-related leukodystrophy comprises a phenotypic spectrum in which the MRI findings range from hypomyelination with atrophy of the basal ganglia and ...

6.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0887899425002875

Critical functional domains in pediatric onset TUBB4A- ...

Original Article. Critical functional domains in pediatric onset TUBB4A-related leukodystrophy: a clinical and caregiver's perspective.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12022754/

The N=1 Collaborative: advancing customized nucleic acid ...

Baseline outcome measures and safety data collection happen concurrently with building a clinical team so that, once approval is granted, the ...