Antisense Oligonucleotide Therapy for Autosomal Dominant Leukodystrophy

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: n-Lorem Foundation

Disqualifiers: Other conditions

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-LMNB1-001, an antisense oligonucleotide therapy, for individuals with autosomal dominant leukodystrophy (ADLD) caused by an LMNB1 mutation. The goal is to determine if this personalized therapy can manage the condition in patients with this specific genetic mutation. Individuals with ADLD due to an LMNB1 mutation who can travel for study visits might be suitable candidates. The trial aims to ensure the treatment's safety and observe the body's response. 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 this new therapy.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research shows that treatments called antisense oligonucleotides (ASOs), such as nL-LMNB1-001, are under study for their safety and effectiveness in treating genetic disorders. Previous studies have found that ASO treatments are generally well-tolerated. Specifically, ongoing research examines the safety of nL-LMNB1-001 for individuals with autosomal dominant leukodystrophy (ADLD).

In trials for similar ASO treatments, participants experienced few serious side effects, suggesting these therapies might be safe for humans. However, since this particular drug remains in the early stages of testing, information about its safety for ADLD is limited. The research aims to determine if any side effects are mild and manageable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for autosomal dominant leukodystrophy, which typically involves managing symptoms and supportive therapies, nL-LMNB1-001 targets the disease at a genetic level. This treatment uses antisense oligonucleotide technology to specifically target and reduce the expression of the LMNB1 gene, which is implicated in this condition. Researchers are excited about nL-LMNB1-001 because it offers a more direct approach to tackling the root cause of the disease, potentially slowing or halting disease progression rather than just alleviating symptoms.

What evidence suggests that this treatment might be an effective treatment for Autosomal Dominant Leukodystrophy?

Research on antisense oligonucleotide therapy, such as nL-LMNB1-001, which participants in this trial will receive, has shown promise in animal studies. In a rat study of a similar genetic condition, this treatment reversed disease symptoms. Although limited information exists for humans, the therapy targets the specific genetic mutation causing Autosomal Dominant Leukodystrophy (ADLD) in participants. This method aims to address the genetic issue at its source, which is why researchers believe it to be effective. Early results suggest this could potentially improve brain function over time. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is specifically for one person with a rare condition called Autosomal Dominant Leukodystrophy (ADLD) caused by an LMNB1 mutation. It's not open to other participants.

Inclusion Criteria

Willingness to follow contraceptive guidance during the intervention period and for at least 40 weeks after the last dose of study intervention

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

I have a genetic condition (ADLD) due to an LMNB1 mutation.

Exclusion Criteria

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Administration of personalized antisense oligonucleotide (ASO) treatment

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• nL-LMNB1-001

Trial Overview The trial is testing a personalized medicine approach using an antisense oligonucleotide drug, nL-LMNB1-001, tailored to treat the genetic mutation causing ADLD in this single participant.

How Is the Trial Designed?

Group I: Open Label Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

n-Lorem Foundation

Lead Sponsor

Trials

5

Recruited

5+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06816498

Personalized Antisense Oligonucleotide Therapy for A ... ... Results Data ... Personalized Antisense Oligonucleotide Therapy for A Single Participant With LMNB1 Mutation Associated Autosomal Dominant Leukodystrophy (ADLD).

2. mayo.edu mayo.edu/research/clinical-trials/cls-20577257

Clinical Trials The purpose of this study is to determine the efficacy and safety of an experimental drug, an anti-sense oligonucleotide (ASO) called nL-LMNB1-001.

3. withpower.com withpower.com/trial/antisense-oligonucleotide-therapy-for-autosomal-dominant-leukodystrophy-44992

Antisense Oligonucleotide Therapy for Autosomal ... Research on antisense oligonucleotide therapy in a rat model of Alexander disease showed promising results in reversing disease symptoms, but specific human ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06816498?intr=antisense%20oligonucleotide&aggFilters=status:act%20rec&rank=8

NCT06816498 | Personalized Antisense Oligonucleotide ... Change in neurological functioning results from baseline at 6-, 12-, 18- and 24-months post nL-LMNB1-001 administration as measured by formal neuro- ...

5. trials.arthritis.org trials.arthritis.org/trials/NCT06816498

Personalized Antisense Oligonucleotide Therapy for a Single ... This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single participant with Autosomal Dominant ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3714349/

Analysis of LMNB1 Duplications in Autosomal Dominant ... Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression.