Antisense Oligonucleotide for Intellectual Disability

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 explores a new treatment called nL-MAPK8-001 (an antisense oligonucleotide) for a specific genetic condition known as Neurodevelopmental Disorder with or without Brain Abnormalities (NEDBA). The goal is to assess how this personalized drug affects participants with a particular MAPK8IP3 gene mutation. The trial is open-label, meaning everyone involved knows the treatment being administered. It suits individuals with a confirmed genetic diagnosis of NEDBA due to a MAPK8IP3 mutation who can travel to the study site. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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 has shown that treatments like nL-MAPK8-001, which use antisense oligonucleotides (ASOs), are being studied for their ability to target specific gene mutations. Promising evidence suggests they can help with genetic disorders, but understanding their safety is crucial.

For nL-MAPK8-001, detailed safety information from previous trials is limited. This trial is in the early stages (Phase 1 and 2), so researchers are still learning about the drug's safety and potential side effects. Early trial phases focus on assessing safety and identifying any side effects.

ASOs are designed to be very specific, which can help reduce unwanted effects. However, like any new treatment, some risks may exist. Participants should discuss these risks with the research team to understand their personal implications. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for intellectual disability, which often focus on managing symptoms or providing supportive therapies, nL-MAPK8-001 targets the condition at a genetic level. This treatment is unique because it uses antisense oligonucleotides, which are designed to specifically bind to and modulate gene expression, potentially addressing the root cause of the intellectual disability. Researchers are excited about nL-MAPK8-001 because it represents a novel mechanism of action that could offer more effective and targeted results than current options.

What evidence suggests that nL-MAPK8-001 might be an effective treatment for Neurodevelopmental Disorder?

Research has shown that treatments like antisense oligonucleotides (ASOs), such as nL-MAPK8-001, can target specific genetic changes that may cause certain disorders. This trial will evaluate nL-MAPK8-001, which targets changes in the MAPK8IP3 gene associated with brain development disorders. Studies have found that targeting similar genetic pathways can improve brain function and reduce symptoms. Although direct data on nL-MAPK8-001's effectiveness is limited, it is designed based on successful methods used in related conditions. This offers hope for its potential to help with intellectual disabilities linked to these genetic changes. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is specifically for one person with a rare condition called NEDBA caused by a unique mutation in the MAPK8IP3 gene. The participant must have intellectual disability due to this genetic change.

Inclusion Criteria

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

Ability to travel to the study site and adhere to study-related follow-up examinations and/or procedures and provide access to participant's medical records

My condition is due to a MAPK8IP3 gene mutation.

Exclusion Criteria

Use of investigational medication within 5 half-lives of the drug at enrolment

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 NEDBA

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-MAPK8-001

Trial Overview The trial is testing an individualized drug, nL-MAPK8-001, which is an antisense oligonucleotide (ASO) designed to target and potentially treat the genetic cause of the participant's neurodevelopmental disorder.

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+

Citations

1. withpower.com withpower.com/trial/phase-2-neurodevelopmental-disorder-with-or-without-variable-brain-abnormalities-1-2025-6121f

Antisense Oligonucleotide for Intellectual Disability This Phase 1 & 2 medical study run by n-Lorem Foundation needs participants to evaluate whether nL-MAPK8-001 will have tolerable side effects & efficacy for ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024067860

RNA-Seq data analysis reveals novel nonsense mutations ... Our study concludes that the decrease in the expression of the NPR3 gene causes delayed sensory, motor, and physiological functions of the human brain.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11947108/

A hyper-activatable CAMK2A variant associated with ... A hyper-activatable CAMK2A variant associated with intellectual disability causes exaggerated long-term potentiation and learning impairments.

4. nature.com nature.com/articles/s41598-025-11617-3.pdf

Guanine is an inhibitor of c-jun terminal kinases Together these data demonstrate that guanine, and maybe adenine directly or indirectly, is an inhibitor of MAPK8-10. Lastly, since MAPK9 promotes translation40 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10952735/

Therapeutic validation and targeting of signalling networks ... We argue that elucidating the signalling and transcriptional networks that are dysregulated in patients will afford new therapeutic opportunities.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6369540/

De Novo Variants in MAPK8IP3 Cause Intellectual ... According to data from ExAC, MAPK8IP3 is a gene with a significantly reduced number of truncating and missense variants in controls ...

7. researchgate.net researchgate.net/publication/330130859_De_Novo_Variants_in_MAPK8IP3_Cause_Intellectual_Disability_with_Variable_Brain_Anomalies

(PDF) De Novo Variants in MAPK8IP3 Cause Intellectual ... Using exome sequencing, we have identified de novo variants in MAPK8IP3 in 13 unrelated individuals presenting with an overlapping.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30612693/

De Novo Variants in MAPK8IP3 Cause Intellectual ... We implicate de novo variants in MAPK8IP3 as a cause of a neurodevelopmental disorder with intellectual disability and variable brain anomalies.

9. mdpi.com mdpi.com/2073-4409/11/1/47

KANPHOS: A Database of Kinase-Associated Neural ... To explore the functionality of the KANPHOS database, we obtained phosphoproteomics data for adenosine-A2A-receptor signaling and its downstream MAPK-mediated ...

10. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/mrd.21342

Eomesodermin, HAND1, and CSH1 proteins are induced ... ... MAPK8/9 inhibitors alone, inhibits the induction of CSH1 by stress. Taken together these data suggest that stress-induced MAPK8/9 and PRKAA1 ...