The University of North Carolina at Chapel Hill will lead a consortium receiving up to $24.8 million to detect and stop some of the world’s most devastating diseases, including Alzheimer’s and pulmonary fibrosis at their earliest molecular stage, years before symptoms appear.
Funded through the Advanced Research Projects Agency for Health (ARPA-H), an agency within the U.S. Department of Health and Human Services, the project will bring together seven universities and industry partner Siemens Healthineers to study the earliest molecular changes associated with protein-misfolding diseases.
The project, called IMPEDE, (Instruct & Modulate Protein Ensembles for Disease Evasion) aims to develop an early-detection biomarker for Alzheimer’s disease, advance preclinical treatments for Alzheimer’s and pulmonary fibrosis, and create tools that could be applied to other protein-misfolding diseases.
The promise of targeting ‘undruggable’ proteins
The research will focus on Alzheimer’s and pulmonary fibrosis, two diseases that remain incurable in part because today’s treatments arrive too late, after harmful protein clumps have already damaged cells. This effort aims to change that timeline entirely, intervening at the first molecular missteps, potentially years before a patient notices a symptom.
“For a century, we’ve fought these diseases after the damage is done,” said Ronit Freeman, PhD, associate professor of applied physical sciences and pharmacoengineering at UNC-Chapel Hill and lead scientist for IMPEDE. “Our team’s focus is about getting there first — finding the earliest signs of trouble and acting before disease ever takes hold. ARPA-H asked for moonshot ideas on an aggressive timeline, and our team answered.”
Diseases such as Alzheimer’s and pulmonary fibrosis begin when proteins fold the wrong way and stick together. The proteins involved have no fixed shape and no stable pocket for a drug to grab, so they have long resisted conventional drug design and are labeled "undruggable." IMPEDE pairs laboratory experiments with computer simulation and artificial intelligence to decode what determines whether one of these proteins stays healthy or commits irreversibly to a disease-causing state.
IMPEDE will answer three questions no existing platform can: where on a disordered protein a therapeutic compound can and should bind, when that site is open for binding, and how fast a drug must act before it closes. The goal, as Freeman puts it, is to “make the undruggable druggable.”
The award, timeline and collaborators
Led by Freeman, the four-year award is funded through ARPA-H’s BIOmolecular Grammar for protein Aggregation Modulation and Intervention, or BIOGAMI, program. BIOGAMI is led by ARPA-H Program Manager Shannon Greene, Ph.D.
The IMPEDE team includes experts from UNC-Chapel Hill, Emory University, the University of California San Diego, the University of Copenhagen, the University of Michigan, the University of Texas at Austin, UNSW Sydney and Siemens Healthineers. Work begins Oct. 1, 2026. The team will share progress as milestones are reached over the course of the project.
An accelerated timeline for an urgent problem
ARPA-H structures its awards as fast-moving, milestone-driven partnerships that unite academic, industry and government teams to pursue high-risk, high-reward goals that would not be attempted through conventional funding. IMPEDE has set an unusually ambitious set of milestones. Within four years the team aims to:
- Deliver to the U.S. Food and Drug Administration a diagnostic biomarker for Alzheimer’s, validated in human specimens and able to detect disease before today’s established biomarkers can.
- Advance preclinical drug candidates for Alzheimer’s and pulmonary fibrosis.
- Publicly release a validated “atlas” that predicts how disordered proteins behave from their sequence. The tool is intended to be applicable to any protein-misfolding disease, not only the two studied here.
Discovery of this kind typically unfolds over a decade or more. Here the target is four years, from decoding protein behavior to an FDA submission, reflecting both the urgency of the need and the confidence ARPA-H has placed in the team. The payoff would be a fundamental shift: from treating the damage these diseases cause to potentially stopping them before they start.
“Ronit is a rockstar—both in the lab and in person. When we met with Siemens Healthineers leadership in Germany she was the star of the show,” said Tommy Sowers, PhD, vice chancellor for innovation, entrepreneurship and economic development and chief innovation officer at UNC-Chapel Hill. “Her research is everything Carolina: collaborative, creative and most importantly impactful for citizens of North Carolina and beyond.”
A North Carolina effort with national reach
Siemens Healthineers, which has a significant presence in North Carolina’s Research Triangle region, brings deep expertise to the project essential to moving a biomarker from the laboratory toward the clinic.
“Siemens Healthineers is contributing industry-leading immunoassay development capabilities that have delivered novel, automated assays in support of patient care at scale," said Gaby Marquardt, head of clinical innovation and technology, Diagnostics, Siemens Healthineers. "Our integrated technical modalities — laboratory testing, in vivo imaging, and healthcare AI — complement the research assets of our academic partners in our collective pursuit to benefit patients and specialist clinicians by enabling earlier and more informed patient care decisions.”
The project also draws on UNC-Chapel Hill’s research core facilities and the state’s innovation network. The effort is expected to support jobs, company formation and improved patient care in North Carolina and beyond.
"This consortium shows what’s possible when biomaterial design, clinical expertise and computational power converge around a single goal: catching neurodegenerative diseases earlier and giving people living with these diseases a different future," said Penny Gordon-Larsen, PhD, vice chancellor of research at UNC-Chapel Hill.
About IMPEDE
IMPEDE is a UNC-Chapel Hill-led research consortium funded by ARPA-H’s BIOGAMI program to detect and correct disease-causing protein misfolding before it causes harm. This project relies on multiscale computer simulation, high-throughput experimentation, preclinical models, and access to patient biospecimens — a full stack no single company or laboratory carries alone.
This research is funded by the Advanced Research Projects Agency for Health (ARPA-H) under Agreement No. 1AY2AX000262. The views, opinions and findings expressed are those of the authors and should not be interpreted as representing the official views or policies of ARPA-H or the U.S. Government.
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