A recent study, after being published in the Journal of Experimental Medicine, has gathered widespread attention from the public. Inside this research, a new protein in the human body, which is known as TIE2, is considered to be responsible and among the major reasons that contribute towards the growth of blood vessel abnormalities. This problem is very likely to have an effect on 1 person among the 200 people. This can lead a person to sufferings like strokes and seizures, even worse, haemorrhages. The neurologists conducted this study. They found ways to offer prevention and treatment to such patients. This makes the research a significant contribution to neuroscience.
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Stopping Cerebral Cavernous Malformation
A team of neuroscientists and researchers at the Perelman School of Medicine, University of Pennsylvania, has identified a protein called TIE2. It is considered a major factor in the development and formation of blood vessel abnormalities inside the human body. These abnormalities are also known as ‘’cerebral cavernous malformation’’ referred to in short as CCMs. However, the researchers have stated that some drugs target TIE2. These can be used as a potential cure. They could stop the formation of CCMs inside the body. The neglected treatment of such patients can lead them towards strokes, or other problems like brain haemorrhages, even seizures.
Research Details
The researchers revealed that the protein known as TIE2 is responsible for connecting two highly important pathways. These pathways are MEKK3 and PI3K. Both make major contributions to the formation of “lesions.” These lesions often highly resemble the shape of small mulberries; their appearance is formed inside the veins and takes place in the central nervous system. All these things make the blood vessels very brittle, along with abnormally extremely thin walls. These types of problems, according to the researchers, are caused by the mutation of one of the three genes. The chances of CCM occurrences are 1/200, which is approximately 0.5%, and in itself a low probability among the people.
If a person comes into contact with this unfortunate situation of CCM formation, the only way to remove it from the body is surgical resection. However, in several cases, the location of these CCMs is inside the brain, which makes them incurable. CCMs cause mutations that hyperactivate a signalling pathway. This pathway is called the MEKK2-KLF2/4 pathway. It occurs in the endothelial cells that line the blood vessel walls.
The recent research by neurologists has shed light upon this hyperactivation, which stimulates a second signalling pathway that involves the enzyme phosphoinositide 3 kinase PI3K. The drugs that work in the prevention of the PI3K pathway can be used for the task of CCMs formation in mice, too. However, as per the research, these types of drugs have severe side effects in the human body and are very likely to be tolerated with much difficulty, especially when the topic comes about long-term treatments of the CCMs.
Major Findings
After conducting a detailed study on the topic, the researchers found that the activities of the TIE2 protein have been enhanced in the surroundings of endothelial cells, not just in humans but also in other species like mouse CCMs. There has been a significant rise in the levels of the TIE2 protein in response to elevated MEKK3 – KLF2/4 signalling, and this, in turn, leads to increased activation of PI3K. The team of researchers found that confronting TIE2 with the help of a small drug known as rebastinb prevented the development of new CCMs in mice.
Author’s perspective
Mark L. Kahn, a professor at Penn and a senior author of the new JEM study, gave a statement regarding their findings. The findings identify TIE2 as an extremely prominent link between the MEKK3-KLF2/4 and PI3K signalling pathways. They also suggest that pharmacologic blockade of the TIE2 protein is likely to provide an endothelial cell-centred approach for the chronic suppression of CCM disease. This approach may have fewer side effects compared with systematic PI3K pathway inhibition. Professor Mark also commented that “determining how endothelial cells augment PI3K signalling downstream of the MEKK3-KLF2/4 pathway could identify more vessel-specific therapeutic strategies for the chronic suppression of CCM growth.
Conclusion
The researchers have successfully found a way. Through this, treatment can be offered to patients suffering from CCM formation. This issue can be solved with a similar drug, which works by confronting TIE2, known as rebastinb. Along with the help of rebastinb, the development of CCMs can also be stopped.
