Antisense Oligonucleotide Therapy for Dentatorubral-Pallidoluysian Atrophy

Age: < 18

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: n-Lorem Foundation

Must not be taking: Investigational medications

Disqualifiers: Other conditions, others

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

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.

How is the drug nL-ATN1-002 different from other treatments for dentatorubral-pallidoluysian atrophy?

nL-ATN1-002 is unique because it uses antisense oligonucleotides, which are small DNA-like molecules designed to specifically target and reduce the production of the mutant protein causing the disease. This approach is different from traditional treatments as it directly targets the genetic cause of the condition, offering a more precise method of treatment. ^{1 2 3 4 5}

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 dentatorubral-pallidoluysian atrophy (DRPLA) due to a heterozygous pathogenic CAG trinucleotide expansion in ATN1

Eligibility Criteria

This trial is specifically for one person with a rare condition called dentatorubral-pallidoluysian atrophy (DRPLA), caused by a certain genetic mutation in the ATN1 gene. The participant must have this exact genetic change to qualify.

Inclusion Criteria

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

I have a genetic condition called DRPLA confirmed by a test.

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

Exclusion Criteria

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

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Administration of personalized antisense oligonucleotide (ASO) treatment for DRPLA

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• nL-ATN1-002

Trial Overview The study is testing an individualized drug, named nL-ATN1-002, which is an antisense oligonucleotide (ASO). This ASO is tailored to target and manage the genetic mutation responsible for DRPLA in that 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+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Findings from Research

Conjugating antisense oligonucleotides (ASOs) to an antibody targeting the transferrin receptor significantly improved their bioavailability to the brain in mouse models of spinal muscular atrophy (SMA).

The 8D3130-ASO conjugate not only enhanced SMN2 gene splicing in the central nervous system but also extended the survival of severely affected SMA mice, highlighting its potential as a therapeutic strategy for neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-oligonucleotide conjugate achieves CNS delivery in animal models for spinal muscular atrophy. Hammond, SM., Abendroth, F., Goli, L., et al.[2023]

A potential RNA-targeted therapy using antisense oligonucleotide ASO7 effectively reduced ATXN2 gene expression in mouse models of spinocerebellar ataxia type 2 (SCA2), leading to delayed onset of disease symptoms and improved motor function.

ASO7 treatment normalized the firing frequency of Purkinje cells and protein levels related to SCA2, demonstrating its efficacy even when administered after the onset of motor symptoms, suggesting a promising approach for neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antisense oligonucleotide therapy for spinocerebellar ataxia type 2. Scoles, DR., Meera, P., Schneider, MD., et al.[2022]

References

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

Antisense therapies for movement disorders. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Antisense therapies in neurological diseases. [2022]

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

Allele-selective inhibition of mutant atrophin-1 expression by duplex and single-stranded RNAs. [2021]

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

Antibody-oligonucleotide conjugate achieves CNS delivery in animal models for spinal muscular atrophy. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Antisense oligonucleotide therapy for spinocerebellar ataxia type 2. [2022]