ARPA-H, which stands for Advanced Research Projects Agency for Health, is an agency within the U.S. Department of Health and Human Services. One of its major projects is called the FRONT program which stands for Functional Repair of Neocortical Tissue.
The FRONT program focuses on repair and regeneration of the neocortex, the largest part of the brain. The neocortex is critical for many aspects of cognition and everyday functioning. The neocortex can be damaged in many ways including stroke, traumatic injury, and neurodegeneration, such as in Alzheimer's disease. Serious damage to the neocortex often causes individuals to be dependent on costly therapies or caregivers and can also lead to related health and medical problems. The FRONT program hopes to alter this pattern by using cutting-edge neurodevelopmental principles and stem cell technology to regenerate brain tissue and restore lost functions.
The FRONT program website includes this quote from Jean Hebert, Ph.D., FRONT’s Program Manager: “No technology exists to repair damaged tissue and fully restore lost function. This will enable millions of individuals with what is currently considered permanent brain damage to regain lost functions”.
The FRONT program recently announced its principal recipient of FRONT program funding. The lead organization will be Sophrosyne Biosciences, who will coordinate and oversee a large 5 year project titled Beyond Supportive Therapy: Restoring Full Function of the Damaged Brain by Regrowing Natural Tissue. The overall budget for this large project has been announced as 178 million dollars.
The FRONT program has announced that “Sophrosyne Biosciences, Inc. together with their partners aim to develop a revolutionary therapeutic to restore lost neocortical function in patients with permanent brain damage from stroke, traumatic brain injury, and neurodegeneration. The team will develop precursor tissue grafts that will mimic normal brain development to generate new, normally structured tissue that integrates with the adult brain, focusing initially on focal motor cortex stroke. The program aims for validated precursor tissue and reproducible graft survival.” The project will work with the Federal Drug Administration and other relevant agencies to bring its discoveries and methodologies to the point of clinical utility.
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second initiative in brain regeneration has more recently (late May, 2026) been announced by ARPA-H. This initiative is titled
Brain Repair of Any Injured Neural Structure (BRAINS) Exploratory Topic.
ARPA-H’s website states “The Brain Repair of Any Injured Neural Structure (BRAINS) Exploratory Topic (ET) is the first effort to generate graftable precursor tissues for multiple parts of the brain – extending beyond the FRONT program's focus on the neocortex. BRAINS goal is to show it is possible to reverse damage and disease in any part of the brain.”
Additional information states “BRAINS ET will target brain regions including, but not limited to, the hippocampus, amygdala, thalamus, hypothalamus, striatum, cingulate cortex, substantia nigra, brainstem, and cerebellum. Together, these areas control movement, balance, mood, autonomic body functions, memory formation, and other critical functions. The BRAINS ET approach will address a wide range of disabilities caused by many forms of brain damage, including aging, congenital diseases, strokes, injuries, tumors, and infections.”
BRAINS will involve smaller but more numerous projects to 1) develop tissue engineering methods capable of generating precursor tissue for a part of the brain other than the neocortex and 2) provide proof-of-concept for surgical engraftment of precursor tissue in preclinical models.
BRAINS represents an ambitious step toward a future in which brain injury and degeneration may be treated through true tissue replacement rather than symptom management alone. Researching the generation of region-specific precursor brain tissue and demonstrating proof-of-concept surgical engraftment in preclinical models will, hopefully, lay the foundation for future clinical trials aimed at restoring lost neurological abilities across many regions of the brain.
