A study published in EMBO Molecular Medicine (Volume 17, Issue 11, pages 3021-3038, 2025) has demonstrated that a four-amino-acid peptide called CAQK (Cysteine-Alanine-Glutamine-Lysine) exhibits significant neuroprotective properties in animal models of traumatic brain injury (TBI). The research was conducted by teams at Aivocode Inc., the Sanford Burnham Prebys Medical Discovery Institute, the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), and the University of California, Davis.

Study Design and Findings

CAQK was originally identified through peptide-phage display screening and reported in a 2016 Nature Communications study as a peptide capable of homing to brain injury sites when delivered intravenously. In that earlier work, it was investigated primarily as a vehicle for targeted drug delivery. The 2025 study reveals that CAQK itself possesses intrinsic therapeutic effects without the need to carry additional drugs.

When administered intravenously in mouse models of moderate to severe TBI, CAQK crossed the compromised blood-brain barrier at injury sites and bound to tenascin-C, an extracellular matrix glycoprotein that is upregulated following brain trauma. The peptide accumulated specifically in damaged brain regions rather than healthy tissue. Treated animals showed reduced lesion size, lower inflammatory markers, decreased apoptosis (cell death), and improved behavioral and cognitive function compared to untreated controls. No toxicity was observed.

The researchers also validated their findings in pig models, where CAQK similarly accumulated in injured brain tissue. Because pig brains are structurally closer to human brains, this cross-species confirmation strengthens the translational potential of the findings.

Clinical Significance

Traumatic brain injury affects approximately 69 million people worldwide each year and is a leading cause of death and disability in people under 40. There are currently no FDA-approved drugs for treating acute TBI. Existing treatment focuses on stabilizing patients by managing intracranial pressure and maintaining blood flow, without directly addressing the secondary injury cascade of inflammation and cell death that follows the initial trauma.

Pablo Scodeller, a co-author from IQAC-CSIC, stated in the published findings: "What's exciting is that, in addition to proving highly effective, it's a very simple compound, a short peptide that is easy to synthesize safely at large scale."

Next Steps

Aivocode Inc. is preparing for Phase I human clinical trials, with pig toxicology and pharmacokinetic studies currently underway. The company was founded by study authors Aman P. Mann, Sazid Hussain, and Erkki Ruoslahti as a spin-off of Sanford Burnham Prebys Medical Discovery Institute. The study was funded by NIH (R43NS112050) and NSF (grants 1548490 and 1660165).

The full study is available open-access at EMBO Molecular Medicine (DOI: 10.1038/s44321-025-00312-5, PubMed ID: 41034343).