Anti-inflammatory and antioxidant substances developed at the Hebrew University of Tel Aviv have been shown to be effective in preventing damage associated with mild brain damage in experiments on model mice
Mild brain injury (mTBI) can be caused by accidents and falls in different areas: at school, on the roads, on the sports fields and on the battlefield, and is mainly common among children, athletes and the elderly. The damage does not bear external signs, but similar to a severe brain injury, it is accompanied by secondary damage to the functioning of the brain, which affects, among other things, memory, behavior and emotions.
Although most symptoms of mild brain damage disappear within a few days or weeks, up to 50 percent of victims experience mental changes, cognitive deficits, and somatic disorders about a year after the injury. These secondary changes result from an increase in glutamate levels, an increase in oxidative stress, activation of astrocytes, breach of the blood-brain barrier, and mainly inflammatory activity accompanied by the death of cells (apoptosis).
"It is known that an external or internal injury activates the inflammatory system, which leads through the activation of stress pathways to cell death and associated cognitive and emotional impairments," explains Prof. Dafna Atlas, from the Department of Biological Chemistry at the Alexander Silverman Institute of Life Sciences of the Hebrew University of Jerusalem.
"Therefore, in order to provide an answer to the treatment of brain damage, it is important to delay the inflammatory process that occurs during the brain injury."
To date, no effective treatment has been found to prevent damage to the brain functions associated with a mild brain injury, but the research group led by Prof. Atlas and in collaboration with researchers from Tel Aviv University, was able to prove that treatment with special molecules recently developed in her laboratory helps protect the brain from the inflammatory process that accompanies the injury.
"Given the necessary dose approximately one hour after the injury, these substances will be able to respond in the protection of brain functions and prevention of damage, both short-term and long-term, that may be caused during a head injury at school, on the sports field, on the battlefield, and in other accidents," explained Prof. Atlas.
In recent years Prof. Atlas has developed in her laboratory small molecules called TXM-Peptides. These molecules mimic the action of the protein Thioredoxin, whose function is to maintain the oxidation state of the cells, and at the same time inhibit the activity of the MAPK enzymes that are activated during oxidative stress. In this way they prevent inflammatory processes that lead to the death of cells.
During oxidative stress, the ASK1 protein associated with thioredoxin is released and activates a series of enzymatic reactions that result in the activation of MAPK enzymes and cause inflammatory processes in the brain cells. The TXM-Peptide molecules are peptides consisting of 3 or 4 amino acid residues that are able to neutralize the action of the ASK1 protein by preventing thioredoxin oxidation, thus preventing the activation of the enzymatic system and actually preventing the inflammatory process and cell death.
In a previous study, Prof. Atlas found that the new molecules prevent inflammatory processes that originate from high levels of blood sugar. The molecule TXM-CB3 showed a significant decrease in the activity of the enzymes in the stress pathways in the brain of mice (link to the article: http://new.huji.ac.il/article/19053).
"Since these molecules combine antioxidant activity with inhibitory activity of enzymes responsible for stress pathways in cells (MAPK), we decided to check whether they can also be useful in preventing inflammation caused by injury," explained Prof. Atlas.
In the new study, published in the journal PLOS One (link), Prof. Atlas tested the effectiveness of the treatment with TXM-CB3 and TXM-CB13 molecules (DY70 provided by One Day - Biotech and Pharma Ltd.) in the case of brain injury. The study found that the same molecules prevent damage to brain functions caused by brain damage.
In the experiments, which were conducted in collaboration with Prof. Hagai Pick and Dr. Renana Bartz-Goldstein from Tel Aviv University, the researchers used a mouse model that mimics a brain injury. In this model, a mild brain injury is caused by dropping a weight and causing a controlled injury. This head injury mimics an injury during a fall during play, sports, or an accident and causes the loss of brain function.
In the experiment, the mice were treated approximately 60 minutes after causing the injury with a very low dose (50 mg per kg) of TXM-CB3 and TXM-CB13. The two substances tested were found to be effective in two behavioral models of visual learning and spatial memory, and restored brain function after seven days and also 30 days after the injury, compared to untreated animals. In addition, both molecules were found to be highly effective in their ability to inhibit the activity level of MAPK enzymes in tissue cultures of human origin after exposure to oxidative stress.
"The results of the study showed that the peptides previously found to be effective as antioxidants, as MAPK inhibitors and as inflammation inhibitors, are also able to protect against a decrease in brain function in brain injury model animals. Another advantage of using peptides is the minimal risk of causing toxic effects, since they consist of amino acids that are the natural building blocks that make up cell proteins, this is in contrast to the use of drugs that are not natural," said Prof. Atlas. "Therefore, TXM-CB3 and TXM-CB13 are promising candidates for treatment to prevent secondary damage that affects brain functions."
The development of TXM-Peptides as a potential drug for the treatment of head injuries for humans requires the continuation of clinical studies.
Link to the study:
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0157064
One response
There have been cases in the past that beyond human trials have shown reproducibility, and there were his. The development of Kupakhson by Musa Zemim was successful.
The development of another drug that was not successful - we will not describe it here for the sake of human dignity. It can happen to anyone.