Functional Repair of Neocortical Tissue

The Advanced Research Projects Agency for Health (ARPA-H), a federal agency under the U.S. Department of Health and Human Services, has launched a new funding initiative titled "Functional Repair of Neocortical Tissue (FRONT)" under its Health Science Futures (HSF) office. The initiative is structured as an Innovative Solutions Opening (ISO), numbered ARPA-H-SOL-25-120, and was officially posted on July 10, 2025. ARPA-H’s core mission is to accelerate better health outcomes by supporting high-impact biomedical and health research to tackle society’s most challenging health problems. Through FRONT, ARPA-H aims to develop a first-in-class tissue graft capable of functionally restoring damaged neocortical tissue, ultimately preparing this solution for human clinical trials. FRONT targets more than 20 million Americans who currently live with chronic neocortical damage caused by neurodegeneration, trauma, or stroke, with a broader global impact on over 200 million individuals. The program seeks to develop curative treatments that go beyond current therapy options like occupational or speech therapy, which offer limited functional recovery. Instead, the program will create a transplantable neocortical precursor tissue using induced pluripotent stem cells (iPSCs) and advanced tissue engineering. This tissue must closely mimic the architecture and functional integration capacity of natural neocortical tissue. FRONT explicitly excludes proposals involving human embryos, fetal tissue, or human-animal chimeric tissues. The grant program is divided into two main technical areas (TAs). TA1 focuses on the generation of transplantable neocortical precursor tissue, including cell-type composition and extracellular matrices. TA2 focuses on optimizing surgical grafting methods and validating functional integration within host tissue, including neural connectivity and behavior recovery metrics in large animal models. All phases are organized into a 5-year timeline across three phases: Phase I (24 months), Phase II (24 months), and Phase III (12 months). Successful proposals will demonstrate metrics like vascularization, integration efficiency, and behavioral restoration. Regulatory milestones include readiness for FDA INTERACT and pre-IND discussions. Applicants must submit a mandatory Solution Summary by August 18, 2025, and full proposals by September 25, 2025. A Proposers’ Day will be held on August 8, 2025, and questions are due by August 27, 2025. Eligible applicants include academic institutions, nonprofit organizations, and for-profit companies, although Federally Funded Research and Development Centers (FFRDCs) are generally not eligible unless specific exceptions apply. Foreign entities are eligible with certain restrictions. ARPA-H prioritizes U.S.-based applicants and requires all applicants to be registered in SAM.gov. Applicants must address ethical, legal, and social implications (ELSI) of the proposed technology, including stakeholder engagement and potential public perception challenges. A designated ELSI representative is required for each project team. Regular reporting is expected, including monthly progress updates, annual summits, and participation in regulatory discussions. Award instruments will be structured as Other Transaction Agreements (OTs), and multiple awards are anticipated. Although cost sharing is not mandatory, it may be proposed where appropriate. Proposals will be evaluated on criteria including scientific and technical merit, alignment with ARPA-H’s mission, ELSI considerations, team capability, and cost realism. Submission must adhere strictly to the formats and templates outlined in Appendices A and B of the solicitation document. The official contact for this funding opportunity is FRONT@arpa-h.gov, and further details and submission guidelines can be accessed through SAM.gov.

Fully adhere to format. Non-conforming submissions may be rejected. Read Appendix A and B closely.