Restoring the Damaged Brain: ARPA-H’s FRONT Program Targets Functional Neocortical Repair
The Advanced Research Projects Agency for Health (ARPA-H) has announced an ambitious new program under its Health Science Futures (HSF) office: the Functional Repair of Neocortical Tissue (FRONT) initiative (ARPA-H-SOL-25-120). This Innovative Solutions Opening (ISO) aims to develop a curative therapy for the 20 million adults in the U.S. suffering from chronic neocortical brain damage, a condition is currently largely untreatable. By restoring brain function through bioengineered neocortical tissue, ARPA-H aims to eliminate the permanent effects of brain damage, reduce the estimated annual cost burden of $800 billion, and help restore affected individuals to their former selves.
Program Overview:
The FRONT program is organized around the development of surgically grafted neocortical precursor tissue that can functionally mature in vivo. This will allow the grafted tissue to integrate into a damaged brain with the ability to restore lost functions such as motor control, vision, and speech. Proposing teams must accomplish both major technical areas (TAs):
TA1: Production of Graft Precursor Tissue
Focuses on creating ex vivo tissue derived from induced pluripotent stem cells (iPSCs) that include the full range of cell types and extracellular components of early neocortical development. The structure and cell-cell contacts of the precursor tissue are expected to match their natural counterparts.
TA2: Optimization of Surgical Engraftment Procedures
Involves evaluation of the tissue model created in TA1, including performing surgical delivery, evaluating host-graft integration, and demonstrating that the new tissue can encode useful information and restore learned behavior in large animal models. This TA is further broken down into two sub-parts:
- TA2a: Grafting procedure and integration – involves development of the surgical procedure and staged demo integration and analyses.
- TA2b: Graft function – involves development of an animal behavior model, grafting procedures and monitoring in developed model, and demonstration of graft functionality, along with pre-IND regulatory engagement with the FDA.
The program is divided into three sequential phases across five years:
- Phase I (24 months): Generation of precursor tissues to match early-stage natural tissue.
- Phase II (24 months): Advance to IND-enabling studies, formalize validated fabrication procedures into regulatory-compliant procedures, perform thorough characterization of draft integration in small and large animal models, and establish a large animal model for testing graft integration.
- Phase III (12 months): Complete behavioral assessments to demonstrate graft functionality and undertake regulatory engagements with the FDA, including INTERACT and pre-IND discussions.
Key Dates for Proposers
Potential proposers should be aware of the following critical milestones (all times Eastern):
- Proposers’ Day (in person): August 8, 2025, 9:00 AM–5:00 PM
- Solution Summaries Due: August 18, 2025, 5:00 PM
- Q&A Deadline: August 27, 2025, 5:00 PM
- Full Proposals Due: September 25, 2025, 5:00 PM
Replacing the Irreplaceable
Brain damage from stroke, trauma, or neurodegeneration has long been considered irreversible. The FRONT program is poised to overturn this assumption with the development of functional, integrative tissue grafts that emulate natural neocortical architecture and behavior. By supporting technologies that could restore cognition, mobility, and independence, ARPA-H is targeting one of the largest unsolved challenges in neuromedicine.
Proposers with expertise in neurobiology, iPSC biology, tissue engineering, electrophysiology, and systems neuroscience are encouraged to submit. If your company has considered applying for federal funding, your federal funding journey starts here. EverGlade Consulting is a national firm that helps organizations win and manage federal awards. We offer services ranging from Pursuit, Proposal and Post-Award support to comply with federal regulations at agencies including BARDA, ARPA-H, NIH, DTRA, JPEO, DOD, DIU, DOE, and DARPA
