Antisense Oligonucleotide for Charcot-Marie-Tooth Disease

Age: Any Age

Sex: Female

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: Baseline to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for Charcot-Marie-Tooth disease type 2D (CMT2D), a condition affecting the nerves and muscles. The study focuses on a personalized antisense oligonucleotide, a type of genetic medicine, called nL-GARS1-001. This treatment is specifically designed for individuals with a unique genetic change in the GARS1 gene. Individuals with a confirmed GARS1 genetic variant and the ability to travel for follow-up visits might be suitable for this study. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

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

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

Research has shown that treatments like nL-GARS1-001, known as antisense oligonucleotides (ASOs), have been tested in people for other conditions and are usually well-tolerated. ASOs are small pieces of DNA or RNA that can prevent certain genes from producing harmful proteins.

In studies with similar ASOs, most participants experienced only mild side effects, such as headaches or slight tiredness, while serious side effects were rare. Since this trial is in its early stages, it primarily focuses on assessing safety. This phase helps identify potential risks and how well participants respond to the treatment.

If a treatment has already received FDA approval for another use, it is often considered reasonably safe. However, each treatment can affect individuals differently. It is important to consult a doctor if there are concerns about joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about nL-GARS1-001 for Charcot-Marie-Tooth (CMT) disease because it uses an innovative approach called antisense oligonucleotide therapy. Unlike traditional treatments that mainly manage symptoms, nL-GARS1-001 targets the genetic cause of the disease, potentially slowing or stopping its progression. This treatment specifically targets and modifies the faulty genes responsible for CMT, offering hope for more effective and long-lasting results.

What evidence suggests that this treatment might be an effective treatment for Charcot-Marie-Tooth disease?

Research has shown that a new treatment called antisense oligonucleotides (ASOs) could help with Charcot-Marie-Tooth disease type 2D (CMT2D). These ASOs target specific gene changes, such as the one in the GARS1 gene linked to this disease. In this trial, participants will receive the investigational treatment nL-GARS1-001, an ASO designed to address these genetic changes. Studies have demonstrated that ASOs can reduce symptoms in animals by lowering harmful proteins that cause nerve damage. Early findings suggest that ASOs may improve movement and slow the disease's progression. Although human studies remain limited, the results are promising and suggest potential benefits for patients with this specific genetic change. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is specifically for one person with a rare condition called Charcot-Marie-Tooth disease type 2D (CMT2D), caused by a unique mutation in the GARS1 gene. The eligibility criteria are not provided, indicating that this study is tailored to an individual's genetic makeup.

Inclusion Criteria

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

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

I have a confirmed GARS1 genetic 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 for a single participant with CMT2D

Baseline to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of quality of life, functional skills, and various safety parameters

24 months

What Are the Treatments Tested in This Trial?

Interventions

• nL-GARS1-001

Trial Overview The trial is testing a personalized medicine approach using an antisense oligonucleotide (ASO) drug named nL-GARS1-001, which has been custom-made to target the specific genetic mutation causing CMT2D 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+

The University of Texas Health Science Center, Houston

Collaborator

Trials

974

Recruited

361,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07226297

Personalized Antisense Oligonucleotide for A Single ... Personalized Antisense Oligonucleotide for A Single Participant With GARS1 Gene Mutation Associated With Charcot-Marie-Tooth Disease Type 2D (CMT2D).

2. nature.com nature.com/articles/s41582-024-01013-2

Antisense oligonucleotide shows potential in Charcot– ... Antisense oligonucleotide treatment has therapeutic potential in a severe form of Charcot–Marie–Tooth disease, according to a new study.

3. reporter.nih.gov reporter.nih.gov/project-details/9921508

RePORT RePORTER - National Institutes of Health (NIH) | Charcot Marie Tooth disease (CMT) is a family of rare inherited peripheral neuropathies. CMT1A accounts for 50% of all CMT and is caused by a 1.4 mB duplication ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2162253125000332

Potential ASO-based personalized treatment for Charcot ... We describe a compound heterozygous patient diagnosed with Charcot-Marie-Tooth disease Type 2S with variants in IGHMBP2.

5. jci.org jci.org/articles/view/96499

PMP22 antisense oligonucleotides reverse Charcot-Marie- ... These data show that ASO1 resulted in a dose-dependent reduction in PMP22 mRNA and reversed motor deficits in symptomatic C22 mice.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK1242/

GARS1-Associated Axonal Neuropathy - GeneReviews - NCBI GARS1-HMSN encompasses the phenotypes also referred to as Charcot-Marie-Tooth neuropathy type 2D (CMT2D) and distal spinal muscular atrophy V ( ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK1358/

Charcot-Marie-Tooth Hereditary Neuropathy Overview - NCBI Charcot-Marie-Tooth (CMT) hereditary neuropathy refers to a group of disorders characterized by a chronic motor and sensory polyneuropathy.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2173580824000476

Clinical practice guidelines for the diagnosis and ... The objective of these guidelines is to offer recommendations for the diagnosis, prognosis, follow-up, and treatment of this disease in Spain.

9. cmtausa.org cmtausa.org/

Charcot-Marie-Tooth Association - Accelerating Research ... CMTA supports the development of new treatments for CMT, improvements in the quality of life for people with CMT, and efforts to find a cure.