Peptide shows significant neuroprotective effect for TBI

A four-amino acid peptide called CAQK has shown neuroprotective effects in animal models of traumatic brain injury, researchers have reported.

When given intravenously shortly after injury in mice and pigs, CAQK specifically targeted damaged brain regions, reducing inflammation, cell death and tissue damage while improving memory and motor function.

A peptide is a short chain of amino acids — the basic components of proteins — which can have therapeutic properties when designed to reach specific tissues.

The research was led by Aivocode, a spin-off of the Sanford Burnham Prebys Institute in San Diego, California, in collaboration with the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) and the University of California, Davis.

“The current interventions for treating acute brain injury aim to stabilise 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,” said Dr Pablo Scodeller, researcher at IQAC-CSIC and co-author of the study.

The compound works by binding to glycoproteins — proteins attached to sugars — that increase in damaged brain tissue after trauma.

Once bound, CAQK accumulates in the injured area and appears to limit the cascade of damaging effects that follow brain injury.

Traumatic brain injury affects around 200 people per 100,000 each year and is typically caused by blows to the head from traffic accidents, workplace incidents or falls.

Current treatment focuses on stabilising patients by lowering intracranial pressure and maintaining blood flow, but no approved drugs exist to stop brain damage or secondary effects such as inflammation and cell death. Existing therapies under investigation require direct injection into the brain, an invasive technique that can lead to complications.

The study builds on earlier work carried out in 2016, when the same research team identified CAQK using a screening method known as peptide-phage display, which isolates molecules that bind to specific tissues.

Initially, CAQK was explored as a carrier to deliver drugs to injured brain regions, but the new findings show the peptide itself has therapeutic effects.

In animal studies, CAQK treatment reduced lesion size compared with control groups. Behavioural and memory tests later showed functional improvement, with no signs of toxicity.

“We observed less cell death and lower expression of inflammatory markers in the injured area, indicating that CAQK alleviated neuroinflammation and its secondary effects,” said Dr Aman P. Mann, the study’s first author.

“Behavioural and memory tests conducted after treatment also showed improvement in functional deficits, with no evident toxicity.”

The ability to deliver CAQK intravenously is considered a key advantage over therapies that require direct injection into the brain — a far more invasive approach.

“What’s exciting is that, in addition to proving highly effective, it’s a very simple compound — a short peptide that is easy to synthesise safely at large scale,” said Dr Scodeller.

“Peptides with these characteristics show good tissue penetration and are non-immunogenic.”