Antisense Oligonucleotide for Dentatorubral-Pallidoluysian Atrophy

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: n-Lorem Foundation

Must not be taking: Investigational medications

Disqualifiers: Lumbar puncture contraindication, others

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

Compensation: Varies

Number of Visits: 3

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called nL-ATN1-002 (an antisense oligonucleotide) for a rare brain disorder known as dentatorubral-pallidoluysian atrophy (DRPLA). The goal is to determine if this treatment can benefit individuals with a specific genetic mutation linked to DRPLA. It targets those diagnosed with DRPLA through symptoms and brain scans, with a confirmed genetic mutation in the ATN1 gene. Participants must be able to travel to the study site and adhere to the follow-up schedule. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants the chance to be among the first to benefit from this innovative therapy.

Do I have to stop taking my current medications for the trial?

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 current medications with the study team.

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

Research shows that antisense oligonucleotides (ASOs), like the one being studied here, are designed to address specific genetic problems. In other studies, ASOs have successfully treated certain conditions. These treatments are usually well-tolerated, but they can sometimes cause side effects.

For nL-ATN1-002, which is being tested for a rare condition called dentatorubral-pallidoluysian atrophy (DRPLA), limited information exists on its effects in humans. The trial is in its early stages, with researchers focusing on its safety. This phase primarily ensures the treatment does not cause harmful effects.

Since this treatment is tailored for one participant, monitoring for any side effects is crucial. Although detailed safety data from previous studies with this exact treatment is lacking, its testing suggests experts consider it potentially safe enough to try. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for Dentatorubral-Pallidoluysian Atrophy, which typically involves managing symptoms with medications like muscle relaxants or antiepileptic drugs, nL-ATN1-002 targets the disease at the genetic level. This treatment uses antisense oligonucleotides, which are designed to bind to and reduce the expression of the mutated ATN1 gene responsible for the condition. By directly addressing the root cause of the disease, researchers hope nL-ATN1-002 could potentially slow or even halt disease progression, offering a more effective approach than the current symptom-focused treatments.

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

Research shows that a type of treatment called antisense oligonucleotides (ASOs), such as nL-ATN1-002, may help treat dentatorubral-pallidoluysian atrophy (DRPLA). This condition results from a specific genetic mutation, and ASOs aim to target and reduce the effects of these mutations. Studies on similar genetic disorders have shown that ASOs can effectively lower harmful protein levels. Although data for DRPLA is limited, early findings suggest this treatment could help slow the disease's progression. The goal is to improve symptoms such as muscle control and cognitive decline by addressing the genetic cause. Participants in this trial will receive nL-ATN1-002 in an open-label format to evaluate its effectiveness and safety. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is specifically for one person with a rare genetic disorder called dentatorubral-pallidoluysian atrophy (DRPLA), caused by a certain mutation in the ATN1 gene. The eligibility criteria are not provided, indicating that this study is highly personalized.

Inclusion Criteria

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

My condition is diagnosed as DRPLA based on symptoms and brain imaging.

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

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

Administration of personalized antisense oligonucleotide (ASO) treatment for DRPLA

24 months

Regular visits every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• nL-ATN1-002

Trial Overview The trial is testing an individualized treatment using an antisense oligonucleotide (ASO) drug named nL-ATN1-002, which has been tailored to target the unique genetic mutation causing DRPLA in the 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+

Hawaii Pacific Neuroscience

Collaborator

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/NCT07221760

Personalized Antisense Oligonucleotide for A Single ... Genetically confirmed Dentatorubral-pallidoluysian atrophy (DRPLA) due to ATN1 mutation. Exclusion Criteria: Use of investigational medication ...

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. 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, ...

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

N=1 Collaborative: advancing customized nucleic acid ... Dentatorubral pallidoluysian atrophy (DRPLA), 2, nL-ATN1-002, Non allele selective RNase H, IT, n-Lorem, Unpublished and provided directly by n ...

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

The N=1 Collaborative: advancing customized nucleic acid ... This guidance, a focus of N1C working groups, aims to include sample INDs, a defined clinical trial pathway, recommendations on outcomes that ...

7. 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 ...

8. withpower.com withpower.com/trial/phase-2-myoclonic-epilepsies-progressive-9-2024-0def9

Antisense Oligonucleotide for Dentatorubral-Pallidoluysian ... This Phase 1 & 2 medical study run by n-Lorem Foundation needs participants to evaluate whether nL-ATN1-002 will have tolerable side effects & efficacy for ...