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

Trial Summary

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.

What data supports the effectiveness of the treatment nL-LMNB1-001 for autosomal dominant leukodystrophy?

The research highlights that antisense oligonucleotide therapy, like nL-LMNB1-001, is an emerging approach in treating leukodystrophies, which are genetic disorders affecting the brain's white matter. While specific data on nL-LMNB1-001 is not provided, the general interest in precision medicine and advances in therapeutic target discovery suggest potential benefits in targeting specific genetic causes of these disorders. ^{1 2 3 4 5}

Is antisense oligonucleotide therapy generally safe for humans?

Research on antisense oligonucleotide therapy in a rat model of Alexander disease showed promising results in reversing disease symptoms, but specific human safety data for this therapy in leukodystrophies is not provided in the available articles. ^{1 6 7 8 9}

How is the treatment nL-LMNB1-001 different from other treatments for autosomal dominant leukodystrophy?

The treatment nL-LMNB1-001 is unique because it uses antisense oligonucleotide therapy, which targets and silences the specific duplicated gene causing the disorder, unlike other treatments that do not address the genetic root of the condition. This approach is novel for autosomal dominant leukodystrophy, as there are currently no standard treatments available for this rare disorder. ^{1 3 5 6 10}

What is the purpose of this trial?

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single participant with Autosomal Dominant Leukodystrophy (ADLD) due to LMNB1 mutation

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

Current Therapeutic Approaches in Leukodystrophies: A Review. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

Evaluating meaningful changes in physical functioning and cognitive declines in metachromatic leukodystrophy: a caregiver interview study. [2023]

3. India pubmed.ncbi.nlm.nih.gov

LMNB1 Duplication-Mediated Autosomal Dominant Adult-Onset Leukodystrophy in an Indian Family. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Emerging treatments for pediatric leukodystrophies. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical and pathological features of an autosomal dominant, adult-onset leukodystrophy simulating chronic progressive multiple sclerosis. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Opening New Horizons in the Treatment of Childhood Onset Leukodystrophies. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Antisense therapy in a rat model of Alexander disease reverses GFAP pathology, white matter deficits, and motor impairment. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Allele-specific silencing as treatment for gene duplication disorders: proof-of-principle in autosomal dominant leukodystrophy. [2023]