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Next Generation Research Grant in ASXL-Related Neurodevelopmental Diseases

American Brain Foundation

Neurodevelopmental disorders affect 10–15% of children in the United States and globally. Forty percent of pediatric neurodevelopmental disorders are monogenic in nature, meaning that changes in a single gene are responsible for impairments in cognition, behavior, communication, motor skills, and multiple organ systems—significantly impacting overall quality of life. Monogenic disorders offer the opportunity to study complex neurodevelopmental disease mechanisms through careful analysis of individual gene functions that underlie these conditions.

Bohring-Opitz, Shashi-Pena, and Bainbridge-Ropers Syndromes are neurodevelopmental disorders caused by mutations in the ASXL1, ASXL2, and ASXL3 genes, respectively. ASXL proteins are members of the Polycomb Repressive De-ubiquitinase (PR-DUB) complex, which serves as a key epigenetic regulator of histone ubiquitination and methylation events with farreaching effects on downstream gene networks involved in neurodevelopment and other organ systems. Disease-causing variants in the ASXL genes are primarily heterozygous nonsense and frameshift mutations that produce severe effects across diverse organ systems, with gastrointestinal, cardiac, and neurological defects among the most prevalent and lifethreatening. Deeper understanding of ASXL gene function and disease mechanisms will contribute critical knowledge toward improving brain health and the function of related organ systems throughout development.

The Next Generation Research Grant in ASXL-Related Neurodevelopmental Diseases is an Early Career Award designed to support high-risk, high-reward translational research on the ASXL genes with strong potential for clinical impact.

Funding Available

The ABF and ARRE Foundation intend to award one Early Career Award of up to USD $120,000 total over two years ($60,000 per year). This grant does not support indirect costs; all funds are expected to go directly toward the proposed project. Final budgets will be subject to review of the proposed work.

The Selection Committee reserves the right to award a lesser amount if the full funding request is deemed unjustified, and to fund additional applications should funds allow. Applicants are encouraged to leverage additional sources of funding and resources to complement, but not overlap with, the work funded through this grant.

AI Based Application Success Predictor

1. Direct relevance to brain and nervous system disease (highest predictor)

This is the strongest success predictor. Competitive projects should directly address a neurological or brain-related condition, such as:

ALS
Epilepsy
Stroke
Parkinson’s disease
Multiple sclerosis
Frontotemporal dementia
Lewy body dementia
Myasthenia gravis
Peripheral neuropathy
Cognitive aging and age-related memory loss

The 2026 award portfolio confirms that ABF supports a broad range of specific brain conditions while seeking research that can advance prevention, treatment, diagnosis, or cures.

2. Strong early-career investigator potential (very high predictor)

The Next Generation Research Grants program is specifically designed to identify and develop outstanding early-career researchers and clinician-scientists. ABF describes recipients as promising researchers whose grants help establish long-term careers in brain research.

Competitive applicants typically demonstrate:

Strong scientific promise
Appropriate research training
Early scholarly productivity
Commitment to neuroscience or neurology
Potential for future independence
A credible long-term research trajectory

3. Innovation and originality (very high predictor)

ABF repeatedly describes the NGRG program as supporting innovative investigations. Strong proposals therefore go beyond incremental extensions of established work and may involve:

Novel disease mechanisms
New biomarkers
Innovative imaging methods
Gene-editing approaches
New therapeutic targets
Advanced brain-mapping technologies
Emerging computational or molecular approaches

The 2026 recipients include projects using CRISPR gene editing, advanced brain stimulation, blood biomarkers combined with MRI, and new approaches to understanding brain immune cells.

4. Potential to improve prevention, diagnosis, treatment, or cures (very high predictor)

ABF's research programs seek progress toward:

Understanding disease causes
Earlier or more accurate diagnosis
Improved treatments
Prevention
Ultimately, cures

A strong proposal should clearly explain how the research could change understanding or management of a brain disease. Even basic or mechanistic research becomes more compelling when the pathway toward future clinical benefit is clear.

5. Strong scientific significance and potential field impact (very high predictor)

Competitive projects address an important unresolved problem rather than a narrow question with limited implications. The strongest applications show potential to:

Solve a major disease-specific knowledge gap
Reveal a new biological mechanism
Improve clinical decision-making
Enable a new treatment strategy
Create tools useful to other researchers

ABF's 2026 award announcement emphasizes studies that provide foundational insight for new treatments, prevention, and cures.

6. Potential for impact across multiple brain diseases (high and distinctive predictor)

This is one of the most distinctive features of the American Brain Foundation.

ABF emphasizes the concept that understanding one brain disease can produce insights relevant to others. Its Cure One, Cure Many approach supports research into shared mechanisms and connections across neurological conditions.

Strong cross-disease projects may investigate:

Neuroinflammation
Protein aggregation
Neurodegeneration
Brain immune mechanisms
Genetic pathways
Shared biomarkers
Common mechanisms of neural injury and repair

A project becomes especially compelling when it can advance one disease while creating knowledge applicable to several others.

7. Rigorous and feasible research design (very high predictor)

Innovation must be supported by a credible scientific plan. Competitive applications generally demonstrate:

Clear hypotheses or research questions
Focused aims
Appropriate methodology
Suitable disease models or patient populations
Robust analysis
Realistic milestones
Access to required resources

Because recipients receive at least two years of funding, the project should have enough ambition to produce meaningful results while remaining achievable within the award period.

8. Strong mentorship and research environment (very high for early-career awards)

Because the NGRG program is designed to build the next generation of brain researchers, the applicant's developmental environment is a major practical predictor.

Strong applications typically demonstrate:

Experienced scientific mentorship
Access to relevant patients, datasets, models, or technology
Appropriate institutional infrastructure
Opportunities to acquire new expertise
A clear pathway toward greater independence

The strongest application shows how the award will develop both the research project and the investigator's career.

9. Potential to establish a sustained career in brain research (very high predictor)

ABF explicitly describes Next Generation Research Grants as foundational funding that helps recipients establish long-term careers in medical research.

Strong candidates should therefore show:

Commitment to the selected disease area
A coherent research trajectory
Potential for future independent funding
A plan to build on the proposed study
Evidence that the award will be career-transformative

10. Precise fit with the disease-specific grant category (high and actionable predictor)

Many NGRG awards are organized around specific neurological diseases and are often supported through partnerships with disease-focused organizations. The 2026 portfolio includes awards in ALS, epilepsy, FTD, stroke, Parkinson’s disease, multiple sclerosis, myasthenia gravis, peripheral neuropathy, Lewy body dementia, and cognitive aging.

A competitive applicant should therefore demonstrate precise alignment among:

The disease category
The scientific question
The applicant's expertise
The project's expected impact

11. Strong relevance to health disparities (very high for neurodisparities awards)

For disease-disparity-focused opportunities, ABF prioritizes research examining how social determinants and biological factors influence brain health, how disparities affect neurological outcomes, and which interventions could reduce inequities.

Strong projects may address:

Unequal access to neurological care
Social determinants of brain health
Diagnostic disparities
Treatment inequities
Underrepresented populations
Interventions that improve neurological health equity

12. Strong potential for future research growth and external funding (high predictor)

Because the NGRG program is designed to establish long-term research careers, competitive projects should provide a foundation for:

Larger federal grants
Disease-specific foundation funding
Multicenter studies
Independent research programs
Future clinical or translational development

The strongest proposal explains not only what will be learned during the award but also what the project will enable next.

Specialties

Neurosciences

Eligibility Requirements

Applications may be submitted by basic, translational, or clinical investigators from U.S. and international public and private non-profit entities, including universities, colleges, hospitals, and laboratories, as well as biotechnology, pharmaceutical, or other for-profit companies.

The principal investigator must hold an MD, PhD, or equivalent terminal clinical degree and be within the first five years of their first full-time faculty (or equivalent independent researcher) position at the time of application submission.

Applicants may submit only one application for this RFA. There is no limit on the number of applications submitted from a single institution.

The American Brain Foundation is committed to supporting research that incorporates a broad range of perspectives and includes study populations that reflect the full spectrum of individual affected by ASXL-related neurodevelopmental diseases. The ABF provides equal opportunities to all applicants without regard to race, religion, color, age, sex, pregnancy, national origin, sexual orientation, gender identity, genetic disposition, neurodiversity, disability, veteran status, or any other protected category under applicable law.

Sponsor Details

Sponsor Institute/Organizations: American Brain Foundation

Sponsor Type: Corporate/Non-Profit

Address: 201 Chicago Ave, Minneapolis, MN 55415

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