Research

General Approach

The Foundation for ARID1B Research (FAR) is committed to finding impactful treatments for all individuals living with ARID1B-RD across the world, regardless of age or genotype.
FAR will explore the utility of the most promising therapeutic modalities to achieve this goal. When a specific modality shows potential in treating ARID1B-RD, the Foundation will work to advance it into clinical trials. To make this possible, FAR will become a hub for translational ARID1B research by forming collaborations with researchers, biopharma companies, and the patients’ community.
This approach follows pathways established by similar parent-led rare disease foundations that harnessed parents’ determination and commitment to significantly accelerate therapeutics development significantly. The implementation of this approach will be guided by FAR's growing scientific advisory board.

ARID1B-RD Therapeutics: Why it Can Work

ARID1B-RD is an excellent candidate for translational research for its (a) genetic makeup, (b) prevalence, and (c) because it has been extensively studied using cutting edge tools.

The Genetic Makeup

  • ARID1B-RD is caused by mutations in a single gene, ARID1B.
  • All known mutations cause loss of function.
  • ARID1B-RD is caused by haploinsufficiency. It means that only of the alleles (gene copies) that code for the ARID1B protein is not functional. The other allele functions normally and can potentially be regulated to increase its protein production using established treatment modalities (e.g., ASOs).
  • ARID1B mutations usually cause minor structural changes in the brain.

The Prevalence

  • ARID1B is a high confidence autism gene.

The Existing Research

ARID1B and its roles in the human brain have been extensively studied in the last decade. Current ARID1B research include:

All the above make ARID1B-RD potentially amenable to established intervention approaches that may be able to change the lives of thousands. Hence, ARID1B-RD can be highly attractive for biopharma investment.

Our Roadmap to ARID1B-RD Therapeutics

Our roadmap involves a parallel two-pronged approach: developing therapeutics and setting the stage for clinical trials. The success of the roadmap relies on meeting the goals of both efforts.

Develop
Therapies

Set the Stage for
Clinical Trials

  1. ▼

    Obtain/Create ARID1B Models

    ARID1B-RD models have already been created and are broadly used:

    • Patients iPSCs
    • Mouse and rat models
    • Brain organoids
  2. ▼

    Study Models To

    • Understand the effects of ARID1B mutations at all relevant levels (i.e., molecular, cellular, and behavioral).
    • Discover potential targets for intervention.
    • Identify robust biomarkers and clinical endpoints.
  3. ▼

    Test Therapeutics on Models

    • Small molecules (approved and experimental drugs).
    • Genetic approaches (e.g., ASOs, gene therapy).
    • Testing their effects on biological and behavioral targets in models.
  4. ▼

    Conduct Safety Studies

    Promising therapeutics are tested to examine possible adverse effects (i.e., toxicity) and explore dosing.

  • ▼

    Create an Accessible Patient Registry

    • Accessible to all those working toward therapeutics.
    • Provide critical information about the difficulties of individuals with ARID1B-RD.
    • Help identify the community’s primary needs.
  • ▼

    Conduct a Natural History Study

    • Extensive repeated measurements of key information.
    • In a time scale adapted to the needs of planned clinical trials.
  • ▼

    Increase Diagnostic Rate

    • There is a striking gap between ARID1B-RD prevalence indications and the number of identified patients.
    • FAR will work to close this gap by increasing awareness and testing availability.

Develop Therapies

○
▽

Study Models

  • Understand the effects of ARID1B mutations at all relevant levels (i.e., molecular, cellular, and behavioral).
  • Discover potential targets for intervention.
  • Identify robust biomarkers and clinical endpoints.
○
▽

Test Therapeutics on Models

  • Small molecules (approved and experimental drugs).
  • Genetic approaches (e.g., ASOs, gene therapy).
  • Testing their effects on biological and behavioral targets in models.
○
▽

Conduct Safety Studies

Promising therapeutics are tested to examine possible adverse effects (i.e., toxicity) and explore dosing.

●
▼

Set the Stage for Clinical Trials

Create an Accessible Patient Registry

  • Accessible to all those working toward therapeutics.
  • Provide critical information about the difficulties of individuals with ARID1B-RD.
  • Help identify the community’s primary needs.
○

Conduct a Natural History Study

  • Extensive repeated measurements of key information.
  • In a time scale adapted to the needs of planned clinical trials.
○

Increase Diagnostic Rate

  • There is a striking gap between ARID1B-RD prevalence indications and the number of identified patients.
  • FAR will work to close this gap by increasing awareness and testing availability.
○

Develop
Therapies

Set the Stage for
Clinical Trials

Pharma Companies Take the Lead

  • Promising therapeutic candidates are identified
  • Necessary data collected
  • Pharma companies will be incentivized to take therapeutics to the clinic.
▼
▼

Clinical Trials for Patients

Clinical trials follow a rigorous series of tests from early, small-scale, Phase 1 studies to late-stage, large scale, Phase 3 studies. If a treatment is successful in one phase, it moves on to the next phase. The primary purpose of a Phase 1 study is to evaluate the safety of a new drug candidate. The purpose of a Phase 2 study is to provide an initial assessment of the drug’s effectiveness and to further assess its safety. Phase 3 study is conducted on a large group of patients to provide final evidence for effectiveness and safety.

Approved Therapeutics

Our Partners

FAR aims to become a hub for translational ARID1B research by forming collaborations with academic researchers, biopharma companies, the patient community, and similar rare-disease advocacy organizations.  
We are deeply committed to knowledge and data sharing.
To collaborate with FAR, please contact us.

Mahzi Therapeutics

Jacobs Lab

Coffin-Siris-Syndrome-Foundation

https://www.youtube.com/watch?v=LTssAqnTMWY

The feasibility of genetic therapeutics for ARID1B-RD - An Interview with Dr. Gijs Santen

Dr. Gijs Santen, a clinical geneticist and researcher in the Leiden University Medical Center (LUMC), is an expert on ARID1B. In the video, he is responding to questions presented by the Foundation for ARID1B Research (FAR) about developing new disease-modifying treatments for ARID1B-RD and the role parents can play in promoting this effort.

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