Personalized Antisense Therapy for Genetic Disorder

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, San Diego

Must not be taking: Investigational drugs

Disqualifiers: 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 explores a new treatment for SCN2A-associated developmental epileptic encephalopathy, a rare genetic condition causing severe epilepsy and developmental delays. The study tests a personalized medicine known as an antisense oligonucleotide, a type of targeted genetic therapy, designed for one specific child. The trial is open to a child with a confirmed genetic mutation related to the condition, whose family can travel to the study site and comply with the required procedures. The treatment under investigation is called nL-SCN2A-002. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering the opportunity to be among the first to receive this new therapy.

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 have used an investigational medication recently.

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

Research shows that the treatment nL-SCN2A-002 targets specific genetic factors linked to SCN2A-associated disorders. Currently, no targeted therapy exists for these disorders, but this treatment aims to reduce harmful genetic activity. Previous studies have shown it is safe for some patients with SCN2A-related conditions, suggesting it might be well-tolerated. However, researchers are still learning about the safety of this personalized treatment, and more research is needed to understand any possible side effects. Participants in clinical trials like this one help gather important information about the treatment's safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for genetic disorders, which often involve managing symptoms, nL-SCN2A-002 offers a more targeted approach. This treatment uses antisense therapy, which works by specifically targeting the genetic mutations causing the disorder. Researchers are excited because this method has the potential to directly address the underlying genetic cause rather than just alleviating symptoms. This could lead to more effective and lasting improvements for patients with genetic disorders.

What evidence suggests that this treatment might be an effective treatment for SCN2A associated developmental epileptic encephalopathy?

Research has shown that a personalized treatment called antisense oligonucleotide (ASO) therapy could help with SCN2A-related conditions. In a study with mice, this therapy proved safe, reduced seizures, and extended the mice's lifespan. Another study found that an ASO drug designed for SCN2A gene mutations was safe and effective in early human trials. The SCN2A gene plays a crucial role in brain function, and changes in this gene can cause serious brain problems, such as epilepsy. This trial will evaluate the investigational treatment nL-SCN2A-002, which aims to correct these genetic changes to improve symptoms. ^{2 4 6 7 8}

Who Is on the Research Team?

Olivia Kim-McManus, M.D.

Principal Investigator

UCSD Rady Children's Hospital

Are You a Good Fit for This Trial?

This trial is for a child with a rare genetic disease called SCN2A developmental epileptic encephalopathy. The child must be able to travel to the study site and have parents or guardians who can consent to treatment and follow-up exams. They need confirmed genetic mutation but cannot have taken any investigational drugs recently.

Inclusion Criteria

Informed consent provided by the participant's parent(s)/guardian(s)

I have a confirmed genetic mutation.

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

Exclusion Criteria

I haven't taken any experimental drugs recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive personalized antisense oligonucleotide (ASO) therapy

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• nL-SCN2A-002

Trial Overview The trial is testing an individualized drug, nL-SCN2A-002, which is an antisense oligonucleotide (ASO) therapy tailored specifically for treating this single pediatric patient's unique form of epilepsy caused by their genetic disorder.

How Is the Trial Designed?

Group I: Open label Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

n-Lorem Foundation

Collaborator

Trials

5

Recruited

5+

Published Research Related to This Trial

The development of antisense oligonucleotide (AON)-mediated exon skipping therapies for rare diseases faces significant challenges, including small patient populations and limited data on long-term safety and efficacy.

AONs often require multiple mutation-specific therapies for a single disease, complicating the development process and necessitating collaboration among stakeholders, including patient organizations and regulatory bodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational and regulatory challenges for exon skipping therapies. Aartsma-Rus, A., Ferlini, A., Goemans, N., et al.[2022]

Citations

1. cirm.ca.gov cirm.ca.gov/our-progress/awards/personalized-antisense-oligonucleotide-therapy-rare-pediatric-genetic-disease-scn2a/

Personalized antisense oligonucleotide therapy for rare ... This first in human phase 1 clinical trial with demonstrated safety, tolerability, and efficacy of a personalized ASO drug for SCN2a genetic disease will ...

2. withpower.com withpower.com/trial/phase-2-genetic-diseases-inborn-1-2024-8082f

Personalized Antisense Therapy for Genetic Disorder In a study using a mouse model, the antisense therapy targeting SCN2A was well tolerated, as treated mice showed reduced seizures and extended lifespan without ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6015533/

Progress in understanding and treating SCN2A-mediated ... Advances in gene discovery for neurodevelopmental disorders have identified SCN2A dysfunction as a leading cause of infantile seizures, autism spectrum disorder ...

4. scn2a.org scn2a.org/positive-step-towards-a-treatment-for-scn2a-gain-of-function-patients/

Positive Step Towards a Treatment for SCN2A Gain-of- ... The SCN2A gene helps regulate neuronal excitability, support brain development, and contribute to learning and memory. Changes in the SCN2A gene ...

5. assets-eu.researchsquare.com assets-eu.researchsquare.com/files/rs-7841195/v1/203035c1e0bd3c376c5f4ac8.pdf

Antisense oligonucleotide therapy for rare pediatric genetic ... nL-SCN2A-002 administration in a participant with SCN2A gene mutation. Endpoints: Primary Endpoint: Quantitative change in baseline at 12 and ...

6. nlorem.org nlorem.org/grant-ref/

Grant References SCN2A Treated Nano-rare Patient · had 21-25 seizures/day x3 days during Coronavirus infection (3/7) requiring emergency rescue seizure medication ...

7. researchsquare.com researchsquare.com/article/rs-7603916/v1.pdf

Diplotype-based expanded use of individualized allele- ... In toto, nL-. SCN2A-002 and -001 had potential applicability in seven of fifteen SCN2A-CND patients (Table 1). Demonstration of safety and ...

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

The N=1 Collaborative: advancing customized nucleic acid ... Baseline outcome measures and safety data collection happen concurrently with building a clinical team so that, once approval is granted, the ...