This month’s research news includes advances in our understanding of the cause of focal cortical dysplasia. This research, conducted by former CURE Epilepsy grantee Dr. Jeong Ho Lee and colleagues, identifies the adenosine signaling pathway as a possible treatment target for this type of epilepsy.  

We also report on two studies investigating possible treatments for epilepsy. In the first study, researchers discovered that a cannabis-like chemical naturally found in the brain may be a possible treatment for epilepsy. In the second study, researchers found that a drug  approved for the treatment of multiple sclerosis may be beneficial in the treatment of a rare form of genetic epilepsy.  

Summaries of these research discoveries and more are below:

Understanding Focal Cortical Dysplasia: Research from a team of scientists including former CURE Epilepsy grantee Dr. Jeong Ho Lee shows how defects in even a small percentage of cells during fetal development can lead to a type of epilepsy known as focal cortical dysplasia (FCD). Using a mouse model of FCD, the researchers found that mutated neurons were overproducing a protein known as adenosine kinase, leading to a decrease in a substance called adenosine and eventually increased excitability in nearby neurons. "While we need to further investigate the relationship between the concentration of adenosine and the increased excitation of neurons, our results support the medical use of drugs to activate adenosine signaling as a possible treatment pathway for FCD," Professor Lee said. 
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Following up on this line of research, CURE Epilepsy is currently funding the work of Dr. Detlev Boison and his colleagues to develop an adenosine kinase inhibitor drug as a potential transformative treatment to prevent the development of epilepsy.

Treating Seizures with Cannabis-Like Chemical: Using advanced imaging techniques in mice, researchers have found that a substance naturally found in the brain, which acts similarly to the main chemical found in cannabis, 
may lead to a possible treatment for epilepsy. This substance called
2 arachidonoylglycerol,or 2-AG, has the beneficial effect of decreasing seizure activity. However, researchers also found that the rapid breakdown of
2-AG which occurs in the brain initiates a cascade of events that result in the disorientation and amnesia that may follow an epileptic seizure. The researchers note that further study could guide the development of drugs that reduce seizures’ strength and reduce their aftereffects. 
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Treating KCNA2-Encephalopathy: Researchers have used a drug approved for the treatment of multiple sclerosis to treat a rare form of genetic epilepsy. This type of epilepsy is caused by a mutation in the KCNA2 gene, which leads to defective potassium channels in the brain. The researchers found that the compound 4-aminopyridine (generic name fampiridine, brand name Ampyra) was effective in reducing disease-related symptoms in 9 of 11 patients carrying this mutation. Though the drug isn’t effective for everyone with this type of epilepsy, the researchers have created a database to reference so that doctors can quickly decide whether the drug is a viable option for a person with a newly diagnosed KCNA2 gene defect. 
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Epilepsy Surgery and Brain Health: Epilepsy surgery may be associated with improvements in overall brain health. A study used advanced imaging techniques to determine whether surgery in patients with mesial temporal lobe epilepsy (mTLE) is associated with reduced “BrainAGE” as a sign of overall brain health. MRI analysis of brain-predicted and chronological age difference (BrainAGE) is thought to provide a surrogate marker of overall brain health; the greater the BrainAGE, the lower the overall brain health. The experiment shows that BrainAGE is greater in patients with refractory (difficult-to-treat) TLE by at least seven years compared to healthy controls and that this difference is reduced after epilepsy surgery. The researchers state that their findings are in line with other work suggesting that earlier surgery may benefit patients with refractory TLE. 
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