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Summary: A small peptide called CAQK, composed of only four amino acids, has demonstrated notable neuroprotective effects on traumatic brain injury models in mice and pigs. When injected intravenously, Caqk travels directly to damaged brain tissue, where overexpressed proteins binds and reduces inflammation, cell death and tissue damage.
The treated animals showed an improved memory and motor function without toxicity, which suggests great potential for safe and non -invasive therapy. Researchers plan to seek the approval of the FDA for clinical trials in humans, which marks an important advance towards medicines based on traumatic brain lesions.
Key facts:
Directed reparation: CAQK is aimed at injured brain areas, reducing inflammation and cell death. Non -invasive therapy: administered intravenously, avoiding risky brain injections. Preclinical success: improved recovery in mice and pigs without toxicity; Human essays are planned.
Source: CSIC
The Advanced Chemistry Team of Catalonia (IQAC) of the Higher Council for Scientific Research (CSIC), under the Ministry of Science, Innovation and Universities, has discovered that a small compound, a peptide formed by four amino acids called CAQK, has an important neuroprotective effect in murine models of traumatic brain injury.
When administered intravenously shortly after an injury in animal models (mice and pigs), Caqk is specifically directed to the damaged areas of the brain, attracted by a protein that is overexpeded in the injured tissue after trauma.
Caqk accumulates in the region marked by this protein and is able to reduce inflammation, cell death and damage to brain tissue. In addition, functional recovery without apparent toxicity improved in mice.
The results, published in the Molecular Medicine magazine, open new possibilities for the treatment of injured areas of the brain.
The study has been led by the company AIVocode (a Spin-Off of the Sanford Burnham Prebys) of San Diego, California, in collaboration with the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) and the University of California, Davis.
AIVOCODE, founded by researchers Aman P. Mann, Sazid Hussain and Erkki Ruoslahti.
Although a specific date has not been set, the fact that CAQK is a short peptide, easy to produce and with good tissue penetration, makes it a strong candidate for drug development.
Traumatic brain injury
Traumatic brain lesion (TBI) is a brain damage typically caused by blows to the head, such as those resulting from traffic accidents, labor incidents or falls. It is estimated that it affects about 200 people per 100,000 inhabitants every year.
Currently, the treatment focuses on stabilizing the patient by reducing intracranial pressure and maintaining blood flow, but there are no approved drugs to curb brain damage or its side effects, such as inflammation or cell death. In addition, the therapies that are investigated require direct injections in the brain, an invasive technique that can cause complications.
“Current interventions for the treatment of acute brain damage are stabilized by the patient reducing intracranial pressure and maintaining blood flow, but there are no drugs approved to stop the damages and side effects of these lesions,” explains Dr. Pablo Scodeller, a researcher at the IQAC-CSIC and co-author of the study.
The great challenge of neurology
Finding a non -invasive way of treating an injured brain is one of the main challenges of neurology. This study advances in that direction, based on previous works carried out by researchers in 2016 and published in Nature Communications.
At that time, the researcher Aman P. Mann, together with Pablo Scodeller, working in the laboratory of Dr. Ruoslahti (main author of both studies) in Sanford Burnham Prebys, discovered a peptide (a small chain of amino acids, the basic components of proteins) that specifically pointed to injured areas of the brain in mice.
The peptide, called CAQK, was identified by a large-scale detection technique known as the presentation of Péptido-Fago, which allows the selection of molecules with affinity for specific tissues. In that previous study, Caqk was used as a “vehicle” to manage medications directly to the damaged area.
However, in their new work, the researchers went a step further and showed that the CAQK peptide itself has therapeutic effects.
To evaluate its therapeutic activity, the peptide was administered for the first time intravenously shortly after a moderate or severe traumatic brain injury, and it was observed that the peptide accumulated in the injured brains of mice and pigs (the latter had brains more similar to humans than to those of mice).
In addition, it was discovered that the peptide joins special molecules called glycoproteins (sugar -linked proteins), which become more abundant after an injury and are part of the extracellular matrix, a support network that surrounds brain cells.
The treatment of mice with traumatic brain injury using this peptide resulted in a reduction in the size of the lesion compared to control mice.
“We observe less cell death and less expression of inflammatory markers in the injured area, indicating that Caqk relieved neuroinflammation and its side effects. The behavioral and memory tests carried out after treatment also showed an improvement in functional deficits, without obvious toxicity,” explains the first author of the study, Dr. Mann.
The study results show that the CAQK peptide can help repair the damaged area, highlighting its possible therapeutic applications after a trauma.
“The interesting thing is that, in addition to being very effective, it is a very simple compound: a short peptide that is easy to synthesize safely on a large scale. Peptides with these characteristics show good penetration in tissues and are not immunogenic,” concludes Scodeller.
Key questions answered:
A: It can be administered intravenously and selectively points to the injured brain tissue without invasive procedures.
A: The peptide binds to specific glycoproteins overexposed after a brain injury, which reduces inflammation and protects neurons.
A: Researchers plan to request the authorization of the FDA soon to begin the phase I clinical tests.
About these research novelties in neuropharmacology and TBI
Author: Pilar Quijada
Source: CSIC
Contact: Pilar Quijada – CSIC
Image: The image is accredited to Neuroscience News.
Original research: open access.
“A neuroprotective tetrapid for the treatment of acute traumatic brain injury” by Aman P. Mann et al. Molecular medicine embo
Abstract
A neuroprotective tetrapid for the treatment of acute traumatic brain injury
Traumatic brain lesion (TBI) is an important clinical problem due to the high incidence and severity of the posterior sequelae. Despite great efforts, there are no clinically approved therapeutic drugs for the treatment of acute TBI patients.
To address this unsatisfied need, we evaluate the activity of the CAQK tetrapy in mice. When administered intravenously shortly after a moderate or severe traumatic brain injury, Caqk accumulates in the injured brain of mice and pigs.
Caqk joins a glycoprotein complex of the extracellular matrix that is positively regulated in the injured brain.
The treatment of mice with TBI with CAQK resulted in a reduction in the size of the lesion compared to control mice.
There was a reduced positive regulation of the glycoprotein complex, less apoptosis and a lower expression of inflammatory markers in the injured area, indicating that Caqk relieves neuroinflammation and consequent secondary lesion.
CAQK treatment also improved the functional deficit in mice with TBI, without manifest toxicity. Our findings suggest that CAQK can have therapeutic applications in TBI.
