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

Trial Summary

What is the purpose of this trial?

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single pediatric participant with SCN2A associated developmental epileptic encephalopathy

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.

What data supports the effectiveness of the treatment nL-SCN2A-002 for genetic disorders?

Antisense oligonucleotides (ASOs), like the treatment nL-SCN2A-002, have been shown to modify gene expression and mRNA splicing, which can be effective for various genetic disorders. The FDA has approved ASOs for ten genetic disorders, and examples like nusinersen and Milasen demonstrate their potential in treating neurodevelopmental disorders by correcting splicing defects. ^{1 2 3 4 5}

Is the antisense therapy nL-SCN2A-002 safe for humans?

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 noticeable side effects compared to untreated mice. ^{6 7 8 9 10}

How is the treatment nL-SCN2A-002 different from other treatments for genetic disorders?

The treatment nL-SCN2A-002 is a personalized antisense therapy, which means it is designed to specifically target and modify the genetic expression related to the disorder, unlike standard treatments that may not address the underlying genetic cause. This approach is unique because it can be tailored to the individual's specific genetic mutation, potentially offering a more effective and precise treatment option. ^{1 11 12 13 14}

Research Team

Olivia Kim-McManus, M.D.

Principal Investigator

UCSD Rady Children's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Antisense Oligonucleotide Therapy for Neurodevelopmental Disorders. [2023]

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

Antisense Oligonucleotide Design and Evaluation of Splice-Modulating Properties Using Cell-Based Assays. [2019]

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

Translational and regulatory challenges for exon skipping therapies. [2022]

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

Evaluating human mutation databases for "treatability" using patient-customized therapy. [2022]

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

Consensus Guidelines for the Design and In Vitro Preclinical Efficacy Testing N-of-1 Exon Skipping Antisense Oligonucleotides. [2023]

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

Antisense oligonucleotide therapy reduces seizures and extends life span in an SCN2A gain-of-function epilepsy model. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

SCN2A-Related Epilepsy: The Phenotypic Spectrum, Treatment and Prognosis. [2022]

8. England pubmed.ncbi.nlm.nih.gov

The phenotypic spectrum of SCN2A-related epilepsy. [2020]

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

Functional and pharmacological evaluation of a novel SCN2A variant linked to early-onset epilepsy. [2021]

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

SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy. [2019]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Towards Personalized Allele-Specific Antisense Oligonucleotide Therapies for Toxic Gain-of-Function Neurodegenerative Diseases. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Arginine-rich cell-penetrating peptide dramatically enhances AMO-mediated ATM aberrant splicing correction and enables delivery to brain and cerebellum. [2021]

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

Oligonucleotide therapeutics in neurodegenerative diseases. [2021]