AUTS2 Research Initiatives
Targeted treatments for AUTS2 syndrome don’t yet exist, but the science is moving quickly.
ARC is investing in a coordinated strategy to bridge the gap between discovery and therapy—by building tools, generating data, and supporting collaboration.
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ARC has partnered with the n-Lorem Foundation to research and discover and develop an individualized antisense oligonucleotide (ASO) therapy for a child with AUTS2 syndrome. n-Lorem has advanced multiple ASO programs into the clinic for individuals with ultra-rare disorders. Dr. Jennifer Bain, a board-certified child neurologist at Columbia University Medical Center and a member of the ARC Scientific and Strategic Advisory Board, serves as the treating physician.
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ARC completed an n=1 study with Unravel Biosciences using nasal swab samples to analyze gene expression and predict potential drug candidates. This drug repurposing approach may offer a faster path to treatment while novel therapies are developed. ARC is now working with its scientific advisors and the global research community to understand these data and prioritize follow-up efforts. For now, these findings are for research use only and are not approved treatments for AUTS2 syndrome.
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To understand how different AUTS2 mutations drive disease and to test potential therapies, researchers need cellular models that accurately reflect human biology. While important progress has been made, existing tools represent only a subset of patient mutations and are often difficult to access.
ARC convened global experts to better understand these gaps and is now advancing the development of new, well-characterized, industry-quality models. Our goal is to make these tools broadly accessible without licensing restrictions to both academic and industry researchers.
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Biological samples from individuals with AUTS2 syndrome and their families are essential to advancing research. ARC partners with COMBINED Brain to collect and bank samples in the United States at the Van Andel Institute, and with the Coriell Institute to support international participation.
Samples are collected, processed, and stored under standardized protocols and made available to qualified researchers worldwide. These resources enable genomic and transcriptomic studies and support the development of cellular models for therapeutic testing. Expanding this biobank is a core part of ARC’s long-term research strategy.
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ARC convenes global researchers to align on priorities, identify gaps, and accelerate collaboration.
Our first summit (April 2026) focused on the current landscape of AUTS2 cell models and key gaps to address. Future summits will explore topics such as:
model development and validation (including cellular and animal models)
evaluation of therapeutic candidates, including those identified through ARC’s collaboration with Unravel Biosciences
Summits will be held multiple times per year, as needed, to drive progress across the field.
AUTS2 Research Tools & Resources
Patient Registry
IRB-approved registry via COMBINED Brain supporting natural history studies, cohort queries, and de-identified data access
Biorepository
Sample collection and storage via COMBINED Brain (U.S., Van Andel Institute) and Coriell Institute (International)
iPSC & ESC Models
Several AUTS2 stem cell lines have been developed and show disease-relevant changes, including reduced AUTS2 levels and microcephaly. These models reflect different patient mutations.
ARC is also funding the development of new, license-free iPSC lines and will share updates as this work progresses.
Learn more including a summary of published models and contact information for researchers.
Mouse Models
Several AUTS2 mouse models have been developed and show features similar to the human condition. For example, Auts2⁺/⁻ mice have about a 50% reduction in Auts2 and display both cognitive and behavioral differences.
A near-term goal for ARC is to improve access to these models. You can explore existing lines here.
Mark Hester, PhD (Nationwide Children’s Hospital) maintains an Auts2del15/+ line.
Mikio Hoshino, MD, PhD (National Center of Neurology and Psychiatry, Tokyo) maintains additional published lines.
Zebrafish Model
Early AUTS2 depletion has been studied in zebrafish and recapitulates disease-relevant features, including microcephaly. As with other AUTS2 models, this system may be useful for evaluating potential therapeutic candidates.
Small Molecule Drug Candidates
Computational analysis using Unravel BioNAV™ has identified potential drug candidates for AUTS2. These candidates are being prioritized for in vitro and in vivo testing.
Screening is complete; evaluation is ongoing.
Patient & Control RNAseq Dataset
Nasal swab-derived RNA from an individual with AUTS2 and an unaffected family member was used to generate gene expression data by Unravel Biosciences.
While AUTS2 primarily affects the central nervous system, published work suggests that disease-relevant gene expression signals may sometimes be detectable in accessible tissues. Consistent with this, prior studies have shown altered AUTS2 expression in lymphoblastoid cells from an individual with a disease-associated mutation.