Published
Ask any rare disease advocate what they want most, and the answer is rarely abstract. They want their child to make it to the next school year without another emergency surgery. They want their spouse to walk across the room with confidence. They want a life measured in family milestones, not medical costs or failed treatments.
Yet for most of the approximately 30 million Americans living with a rare disease, that hope runs into the hard limits of today’s healthcare system: delayed diagnoses, scattered data, and too few treatments.
At ARPA-H, we believe that’s not good enough.
Collectively, rare and ultrarare diseases are a large group of disorders that impact a staggering one in ten Americans. Because each disease is unique, it is hard for doctors to correctly distinguish a rare condition from more common ones. Even when a diagnosis is certain, the majority of these disorders have no approved treatments.
The challenge of rare diseases requires a multipronged approach. The research portfolio at ARPA-H is urgently tackling problems of diagnosis, monitoring, and drug development. Our nimble programs are designed to rapidly move from idea to prototype to products that doctors, patients, and families can use.
A sample of our current rare disease-focused programs and projects includes:
BIOGAMI
Repairing misfolded proteins at the root of disease
Many devastating conditions—including some rare diseases—are driven by proteins that misfold inside cells and can no longer do their job.
“We typically think about the link between protein dysfunction and misfolding in well-known diseases such as Alzheimer’s disease and Parkinson's. But protein dysfunction also drive rare disease, like Alpha-1-antitrypsin deficiency and MUC1 Kidney Disease. BIOGAMI will develop the tools to correct or control for the misfolding of any disordered protein.”
— Shannon Greene, Ph.D., ARPA-H Program Manager
The BIOmolecular Grammar for protein Aggregation Modulation and Intervention (BIOGAMI) program will take on the challenge of repairing misfolded proteins and thereby correcting disease. By learning how to repair and stabilize misfolded proteins, BIOGAMI could open entirely new therapeutic options for serious diseases that currently have none, such as amyotrophic lateral sclerosis (ALS), some cancers, and other degenerative conditions.
LIGHT and GLIDE
Putting the lymphatic system on the map
The lymphatic system quietly underpins the health of nearly every organ, yet lymphatic diseases have historically been underdiagnosed, undertreated, or misunderstood. For many rare lymphatic disorders, patients and clinicians have had to rely on crude tools and lifelong symptom management rather than true disease modification.
The Lymphatic Imaging, Genomics, and Phenotyping Technologies (LIGHT) program is funding teams working on improved ways to diagnose lymphatic dysfunction. Because improving our diagnostic tools is critical to getting ahead of many chronic and/or rare disorders.
The Groundbreaking Lymphatic Interventions and Drug Exploration (GLIDE) program is building brand new tools to treat lymphatic disorders that underly some rare diseases. The program aims to replace compression therapy with treatments that do more than just manage symptoms. New techniques could instead repair lymphatic dysfunction and restore healthy function.
For families of those suffering from lymphatic disease, this research is profound.
“As a parent of a child with a rare lymphatic disease, what moves me most is that LIGHT and GLIDE put patients at the center as mandatory partners: our Discovery Duos. This ensures families like mine who live this reality every day are shaping the science that will move us from a lifetime of managing symptoms to actually curing disease. Because 'palliative and lifelong' is simply not good enough."
— Kim Steele, M.D., Ph.D., ARPA-H Program Manager
RAPID
Ending the diagnostic odyssey
The search for rare disease diagnosis stretches often on for years. During that time, families see multiple specialists, undergo repeated testing, and still lack clear answers. ARPA-H's Rare Disease AI/ML for Precision Integrated Diagnostics (RAPID) program aims to change that.
"RAPID aims to end the rare disease diagnostic odyssey by developing integrated, AI- enabled systems that support early, accurate, and scalable identification of rare diseases. The program will build the largest curated longitudinal rare disease dataset, powering novel tools to increase access to specialist expertise and confirmatory testing, reduce avoidable costs, and promote development of new treatments."
— Scott Gorman, J.D., MBA, ARPA-H Program Manager
RAPID will develop AI-based detection models to accurately diagnose rare diseases radically faster than ever before. Earlier diagnosis can mean earlier intervention, better quality of life, and more time for and new therapies to make a difference.
THRIVE
Making precision genetic medicines available to all
Many rare diseases are rooted in specific genetic changes. Precision genetic medicines—genome editing and gene therapies—have shown that it is possible to address those changes at their source. But current approaches are often bespoke, expensive, and time-consuming to develop, limiting how many patients can benefit.
The Treating Hereditary Rare Diseases with In Vivo Precision Genetic Medicines (THRIVE) program aims to flip that equation.
“THRIVE aims to create commercially viable and platformizable precision medicines that will reach many rare disease patients. THRIVE will advance innovative methods for genome editing and gene therapy and enable new regulatory pathways for faster approvals.”
— Daria Fedyukina, Ph.D., ARPA-H Program Manager
MATRIX
Accelerating new uses for existing drugs
Even as new medicines are developed, thousands of existing drugs sit on pharmacy shelves with potential that has not yet been fully explored. Many of these medicines may hold promise for rare and underserved conditions—but finding the right match between drug and disease is a massive search problem.
The ML/AI-Aided Therapeutic Repurposing In eXtended uses (MATRIX) project is tackling that challenge.
“MATRIX is building an AI-powered platform that searches across every approved drug and every known disease to find new uses for existing medicines. By rapidly validating the most promising matches and continuously refining its prediction models, MATRIX aims to reduce the time and cost of bringing new treatments to rare and underserved conditions.”
— Scott Gorman, J.D., MBA, ARPA-H Program Manager
PCX
Building a nationwide pediatric precision medicine network
Pediatric cancer is the leading disease-related cause of death in children—but it still qualifies as a rare disease, affecting fewer than 200,000 kids per year in the United States. For families, access to cutting-edge diagnostics and treatments can depend heavily on where they live.
The Pediatric Care eXpansion (PCX) effort is designed to change that equation. With $50 million in funding, PCX is expanding pediatric cancer care across more than 200 health centers nationwide and is part of ARPA-H’s Biomedica Data Fabric Toolbox, a broader initiative focused on interoperable data exchange.
“A defining feature of PCX is that it pulls together comprehensive data into a nationwide network for children's care. This lets doctors pull real-time genetic insights into clinical decision-making for children with complex diseases, like rare cancers. PCX is built to scale this precision medicine infrastructure across 200+ hospitals—so that every child can benefit from data-driven, personalized care.”
— Erika Kim, Ph.D., ARPA-H Program Manager
PCX is part of ARPA-H's Biomedica Data Fabric Toolbox program, a larger effort explicitly focused on interoperable data exchange.
Patients are partners, not bystanders
Patient engagement is a key part of any work in rare disease. Programs like LIGHT, GLIDE, RAPID, and THRIVE require direct involvement from patient groups. This collaboration ensures ARPA-H technologies are meeting the needs of families.
As Kim Steele’s experience underscores, putting patients at the center changes both the questions researchers ask and the solutions they pursue. It is how ARPA-H aims to ensure that “palliative and lifelong” is no longer the default for rare disease care.
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