Migraines are debilitating chronic headaches that can cause pain for hours or days. Migraines can begin in the early teen years and may be triggered by many things, including stress, odors, certain foods, alcohol, etc. Some migraines are accompanied by visual disturbances called auras, which are characterized by sensitivity to light, scintillating shapes, sometimes nausea and vomiting. About a third of migraine attacks are preceded by an aura.
In 2010, an international study ("A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura." Nature Medicine, September, 2010. doi:10.1038/nm.2216) led by scientists at Montreal University and the University of Oxford, identified a gene associated with common migraines with aura. Using DNA samples from several generations of a large family who had been suffering from migraine with aura, the researchers were able to identify the mutation on a gene known as KCNK18 or TRESK that was common to the members of the immediate family. TRESK normally plays a key role in nerve cell communication. The mutation investigated results in an incomplete TRESK protein, which disrupts the normal functioning of this potassium channel protein. The end result is an alteration in the excitability of nerve cells in the CNS. When this gene doesn't work as it should, a migraine attack is more easily brought on by migraine triggers. This leads to the exciting conclusion that a migraine headache is a nerve excitability problem, and now the key causal pathway is known, in a general way. TRESK is abundant in migraine-related areas, such as the trigeminal ganglia. The research suggests that restoring TRESK activity through drug intervention may mitigate the severity or frequency of migraine headaches.
The study's lead author, Dr. Ron Lafreniere, said, "When we tested everyone in the family, all those who suffered from migraines also had the mutation." This is a very important scientific discovery, because it has the potential of providing a better understanding of the ultimate cause of migraines and their pathology, as well as the development of new treatments. In the paper's conclusion, it was stated "up-regulating TRESK activity with agonists could be of great benefit for migraine sufferers, either as an acute treatment or as a long-term prophylactic."
In 2010, an international study ("A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura." Nature Medicine, September, 2010. doi:10.1038/nm.2216) led by scientists at Montreal University and the University of Oxford, identified a gene associated with common migraines with aura. Using DNA samples from several generations of a large family who had been suffering from migraine with aura, the researchers were able to identify the mutation on a gene known as KCNK18 or TRESK that was common to the members of the immediate family. TRESK normally plays a key role in nerve cell communication. The mutation investigated results in an incomplete TRESK protein, which disrupts the normal functioning of this potassium channel protein. The end result is an alteration in the excitability of nerve cells in the CNS. When this gene doesn't work as it should, a migraine attack is more easily brought on by migraine triggers. This leads to the exciting conclusion that a migraine headache is a nerve excitability problem, and now the key causal pathway is known, in a general way. TRESK is abundant in migraine-related areas, such as the trigeminal ganglia. The research suggests that restoring TRESK activity through drug intervention may mitigate the severity or frequency of migraine headaches.
Genes involved in moving salts through a nerve membrane are called ion channel or "transporter" genes. Recent research has shed light on two-pore-domain Potassium (K2P) channels as a highly regulated and diverse superfamily of ion channels that are thought to provide baseline regulation of nerve membrane excitability. Of these, the "tandem pore domain potassium" (or TREK) channels are expressed highly in the human central nervous system (CNS), and can be activated by temperature, membrane stretch, and acidity.
Now that a gene defect leading to a common form of migraine headaches has been identified and sequenced, a pill to prevent migraine headaches could be coming in a few years. If drugs can be explored which increase TRESK activity in affected individuals, then this may reduce the sensitivity of the critical CNS nerve cells, which in turn could reduce the likelihood of migraine. So, new drug-based migraine treatments could be developed, based on these important discoveries.
According to Dr. Guy Roleau of the CHU Sainte-Justine Research Center of the University of Montreal, part of the international team, "We may be moving toward developing a pill that would block the brain's pain channel that reacts to stimulation and causes pain in migraine...Sequencing the gene not only allows us to understand the disease - it also opens understanding of the pain pathways that trigger migraine pain." Dr. Roleau also is hopeful that, for the first time since the discovery of triptans in the 1980's, researchers may be able to develop preventive drugs for migraine headaches.
The discovery of a gene for aura migraines in 2010 confirms the common observation that migraine is very common in some families, and the proof now that a genetic factor in migraine auras is at work here is an important advance in understanding the biochemical and metabolic basis of migraine treatment.
In 2010, an international study ("A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura." Nature Medicine, September, 2010. doi:10.1038/nm.2216) led by scientists at Montreal University and the University of Oxford, identified a gene associated with common migraines with aura. Using DNA samples from several generations of a large family who had been suffering from migraine with aura, the researchers were able to identify the mutation on a gene known as KCNK18 or TRESK that was common to the members of the immediate family. TRESK normally plays a key role in nerve cell communication. The mutation investigated results in an incomplete TRESK protein, which disrupts the normal functioning of this potassium channel protein. The end result is an alteration in the excitability of nerve cells in the CNS. When this gene doesn't work as it should, a migraine attack is more easily brought on by migraine triggers. This leads to the exciting conclusion that a migraine headache is a nerve excitability problem, and now the key causal pathway is known, in a general way. TRESK is abundant in migraine-related areas, such as the trigeminal ganglia. The research suggests that restoring TRESK activity through drug intervention may mitigate the severity or frequency of migraine headaches.
The study's lead author, Dr. Ron Lafreniere, said, "When we tested everyone in the family, all those who suffered from migraines also had the mutation." This is a very important scientific discovery, because it has the potential of providing a better understanding of the ultimate cause of migraines and their pathology, as well as the development of new treatments. In the paper's conclusion, it was stated "up-regulating TRESK activity with agonists could be of great benefit for migraine sufferers, either as an acute treatment or as a long-term prophylactic."
In 2010, an international study ("A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura." Nature Medicine, September, 2010. doi:10.1038/nm.2216) led by scientists at Montreal University and the University of Oxford, identified a gene associated with common migraines with aura. Using DNA samples from several generations of a large family who had been suffering from migraine with aura, the researchers were able to identify the mutation on a gene known as KCNK18 or TRESK that was common to the members of the immediate family. TRESK normally plays a key role in nerve cell communication. The mutation investigated results in an incomplete TRESK protein, which disrupts the normal functioning of this potassium channel protein. The end result is an alteration in the excitability of nerve cells in the CNS. When this gene doesn't work as it should, a migraine attack is more easily brought on by migraine triggers. This leads to the exciting conclusion that a migraine headache is a nerve excitability problem, and now the key causal pathway is known, in a general way. TRESK is abundant in migraine-related areas, such as the trigeminal ganglia. The research suggests that restoring TRESK activity through drug intervention may mitigate the severity or frequency of migraine headaches.
Genes involved in moving salts through a nerve membrane are called ion channel or "transporter" genes. Recent research has shed light on two-pore-domain Potassium (K2P) channels as a highly regulated and diverse superfamily of ion channels that are thought to provide baseline regulation of nerve membrane excitability. Of these, the "tandem pore domain potassium" (or TREK) channels are expressed highly in the human central nervous system (CNS), and can be activated by temperature, membrane stretch, and acidity.
Now that a gene defect leading to a common form of migraine headaches has been identified and sequenced, a pill to prevent migraine headaches could be coming in a few years. If drugs can be explored which increase TRESK activity in affected individuals, then this may reduce the sensitivity of the critical CNS nerve cells, which in turn could reduce the likelihood of migraine. So, new drug-based migraine treatments could be developed, based on these important discoveries.
According to Dr. Guy Roleau of the CHU Sainte-Justine Research Center of the University of Montreal, part of the international team, "We may be moving toward developing a pill that would block the brain's pain channel that reacts to stimulation and causes pain in migraine...Sequencing the gene not only allows us to understand the disease - it also opens understanding of the pain pathways that trigger migraine pain." Dr. Roleau also is hopeful that, for the first time since the discovery of triptans in the 1980's, researchers may be able to develop preventive drugs for migraine headaches.
The discovery of a gene for aura migraines in 2010 confirms the common observation that migraine is very common in some families, and the proof now that a genetic factor in migraine auras is at work here is an important advance in understanding the biochemical and metabolic basis of migraine treatment.
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