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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for dentatorubral-pallidoluysian atrophy (DRPLA), a rare brain disorder caused by a specific genetic change. The treatment uses a personalized drug called nL-ATN1-002, which targets the genetic mutation at the root of DRPLA. Individuals with a confirmed diagnosis of DRPLA due to an ATN1 gene mutation can participate. Participants must travel to the study site and attend all necessary appointments and procedures. As a Phase 1 trial, this 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.

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

Research shows that treatments like nL-ATN1-002 are being tested for safety in treating rare conditions such as dentatorubral-pallidoluysian atrophy (DRPLA). These treatments aim to target and silence specific genetic mutations. Previous studies on similar treatments have found them generally safe for patients. However, as with any new treatment, monitoring for side effects is crucial. Since this trial is in its early stages, the primary focus is on ensuring the treatment's safety for humans. While there is limited information on long-term effects, early research appears promising. Prospective participants should discuss any concerns with the medical team involved. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for DRPLA?

Researchers are excited about nL-ATN1-002 for treating Dentatorubral-Pallidoluysian Atrophy (DRPLA) because it uses a unique approach called antisense oligonucleotide therapy. Unlike current treatments that mainly focus on managing symptoms, nL-ATN1-002 targets the root cause by specifically blocking the mutant ATN1 gene responsible for DRPLA. This innovative mechanism of action offers the potential to slow or stop disease progression, which is a significant advancement over existing therapies.

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

Research has shown that antisense oligonucleotides (ASOs) can target and reduce harmful genetic material linked to certain diseases. In this trial, the antisense oligonucleotide treatment nL-ATN1-002 is specifically designed for dentatorubral-pallidoluysian atrophy (DRPLA), a rare genetic disorder. This treatment aims to lessen the effects of a genetic mutation in ATN1, which causes DRPLA symptoms like movement problems and cognitive decline. Early research and similar ASO therapies for other conditions have shown promise in slowing disease progression and improving symptoms. Although this is a personalized treatment for one participant, the approach suggests it could effectively address the root cause of DRPLA. ^{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 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 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 for DRPLA

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-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.

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+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Published Research Related to This Trial

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]

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07084311

Personalized Antisense Oligonucleotide for A Single ...

Clinical phenotype and neuroimaging consistent with a diagnosis of ATN1 mutation associated Dentatorubral-pallidoluysian atrophy (DRPLA).

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06706388

Personalized Antisense Oligonucleotide Therapy for a ...

Genetically confirmed Dentatorubral-pallidoluysian atrophy (DRPLA) due to ATN1 mutation. Exclusion Criteria: Use of investigational medication within 5 half ...

3.

patlynk.com

patlynk.com/trial/NCT07221760

Experimental Antisense Oligonucleotide for DRPLA with ...

This clinical trial focuses on evaluating a new treatment approach for a rare genetic disorder called Dentatorubral-pallidoluysian Atrophy ...

4.

academic.oup.com

academic.oup.com/nar/article/53/8/gkaf346/8119804

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

Initially focusing on antisense oligonucleotides (ASOs) for rare, fatal neurodegenerative conditions, the N1C aims to develop frameworks that ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11075437/

a patient organization perspective

Dentatorubral-pallidoluysian atrophy (DRPLA) is an ultra-rare neurodegenerative disorder characterized by ataxia, cognitive decline, myoclonus, ...

6.

trial.medpath.com

trial.medpath.com/clinical-trial/976ad1a3d2426cfd/nct07221760-experimental-antisense-oligonucleotide-treatment-drpla-atn1-mutation

Personalized Antisense Oligonucleotide for A Single ...

This is an interventional study to evaluate the safety and efficacy of treatment with an individualized antisense oligonucleotide (ASO) treatment in a ...