A global research team led by the company Aivocode, working with scientists from the Institute for Advanced Chemistry of Catalonia (IQAC) of the Spanish National Research Council (CSIC), reports that a small compound has a strong protective effect in mouse models of traumatic brain injury. The compound is a peptide made from four amino acids called CAQK.
In animal tests (mice and pigs), researchers gave CAQK through an IV soon after injury. The peptide was drawn to damaged parts of the brain because it is attracted to a protein that becomes unusually abundant in injured tissue after trauma. CAQK built up where this protein was concentrated and helped reduce inflammation, cell death, and harm to brain tissue. In mice, the treatment also improved functional recovery and showed no obvious toxicity.
Study details and plans for human trials
The findings were published in EMBO Molecular Medicine and point to new ways to treat injured brain regions. The work was led by Aivocode (a spin-off of the Sanford Burnham Prebys Institute) in San Diego, California, in partnership with IQAC-CSIC and the University of California, Davis.
Aivocode was founded by researchers Aman P. Mann, Sazid Hussain, and Erkki Ruoslahti (authors of the study). The company says it plans to seek permission from the U.S. Food and Drug Administration (FDA) to begin Phase I clinical trials in humans. No timeline has been announced, but CAQK’s small size matters because it is a short peptide that is easier to manufacture and can penetrate tissue well, making it a promising drug candidate.
Traumatic brain injury and the lack of approved drugs
Traumatic brain injury (TBI) usually happens after a blow to the head, including injuries from traffic crashes, workplace accidents, or falls. It is estimated to affect around 200 people per 100,000 inhabitants each year. Today’s care focuses on keeping patients stable by lowering intracranial pressure and preserving blood flow, yet there are no approved medicines that stop the brain damage itself or the secondary cascade that follows, including inflammation and cell death. Some experimental approaches also require direct injections into the brain, which is invasive and can lead to complications.
“The current interventions for treating acute brain injury aim to stabilize the patient by reducing intracranial pressure and maintaining blood flow, but there are no approved drugs to stop the damage and secondary effects of these injuries,” explains Dr. Pablo Scodeller, researcher at IQAC-CSIC and co-author of the study.
A non-invasive approach and a key link to earlier research
Developing a non-invasive treatment for an injured brain remains one of neurology’s biggest challenges. This study builds on earlier research from 2016 that was published in Nature Communications.
In that earlier work, researcher Aman P. Mann and Pablo Scodeller, working in Dr. Ruoslahti’s lab at Sanford Burnham Prebys (senior author of both studies), identified a peptide that could home in on injured areas of the mouse brain. The peptide, CAQK, was found using peptide-phage display, a large-scale screening method that helps researchers select molecules that bind to specific tissues. At the time, CAQK served mainly as a “vehicle” to carry drugs directly to the injured region. The new study shows something more, that CAQK itself can have therapeutic effects.
How CAQK targets damaged tissue in mice and pigs
To test whether CAQK could work as a treatment, the team administered it intravenously soon after a moderate or severe traumatic brain injury. They then saw the peptide accumulate in injured brain tissue in both mice and pigs (the latter having brains more similar to humans than mice). The researchers also found that CAQK binds to glycoproteins (proteins attached to sugars), which increase after injury and are part of the extracellular matrix — a supportive structure that surrounds brain cells.
When mice with traumatic brain injury received CAQK, their lesion sizes were smaller than those in control mice. “We observed less cell death and lower expression of inflammatory markers in the injured area, indicating that CAQK alleviated neuroinflammation and its secondary effects. Behavioral and memory tests conducted after treatment also showed improvement in functional deficits, with no evident toxicity,” explains the study’s first author, Dr. Mann.
The results suggest that CAQK can support repair in damaged brain tissue and may have therapeutic value after trauma. “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. Peptides with these characteristics show good tissue penetration and are non-immunogenic,” concludes Scodeller.
