Potential disease-altering treatment for epilepsy

Epilepsy brain centres
Potential treatment for epilepsy could alter disease mechanism Source: FatemehT (via Pixabay)
Scientists at the University of Illinois at Chicago have found a potential disease-altering treatment for epilepsy involving targetting a specific molecule.

By Mili Jayadeep | Science Editor

Epilepsy is a medical condition affecting the brain and can originate in specific areas known as epileptic centres. Spontaneous bursts of electrical energy arising in neurons in these centres is abnormal and can disrupt normal brain function. Epilepsy can present in different forms; it can cause seizures, which can affect one’s state of consciousness, can cause ‘fitting’, characterized by jerking and shaking and even result in weird sensations in the body. This neurological condition typically affects children or older adults over the age of 60. However, it can affect people regardless of ethnicity or gender. The causes of epilepsy may be unclear but it is hypothesised that having a family history of epilepsy can contribute to its manifestation. On the other hand, it can be a result of structural damage to the brain from a stroke, brain tumour or substance abuse, to name a few examples. 

Scientists at the University of Illinois at Chicago (UIC) have discovered a potential disease-altering treatment for epilepsy. Their findings were published in the journal, Neurobiology of Disease. UIC Professor, head of neurology and rehabilitation and co-author of the study,  Dr. Jeffrey Loeb and colleagues studied the involvement of a protein molecule known as DUSP4 in normal neuronal functioning. Their research showed that DUSP4 was present in higher quantities in healthy brain tissue than in epileptic tissue. Their approach focuses on increasing DUSP4 levels in epileptic brain tissue to return normal brain function.

Dr. Loeb explains the purpose of their research,

“If epileptic brain regions spread throughout the brain with nothing to stop them, the seizures would overwhelm the brain, it would not be survivable…We wondered if there were natural ways that epileptic brain areas are quarantined. We searched for genes at the border between epileptic and normal brain tissue that may help prevent the spread of epilepsy.”

 The team studied the genes in the surgically removed tissues of 20 epileptic patients. The tissue included epileptic tissue samples as well as normal tissue surrounding the abnormal brain tissue. Using mathematical modelling, they analysed and compared the genes present in both normal or abnormal tissue.

Earlier research conducted also pinpointed a signalling cascade known as the mitogen-activated protein kinase pathway(MAPK) that was amplified in people with epilepsy. Experimenting on animal models revealed that inhibiting this pathway decreased electrical activity associated with epilepsy. Dr. Loeb says,

 “We were excited about DUSP4 because it is known to be a potent MAPK pathway inhibitor in cancer cells…Seeing this gene activated at the borders and shutting off MAPK signaling genes in the human brain led us to believe that the protein cordons off epileptic regions so that they don’t enlarge or spread, similar to how in a ship you might get a leak in one area, but you can close and seal off doors to keep the leak isolated. That’s how we think DUSP4 is working to keep epileptic focal points from enlarging.”

The scientists studied the protein levels in the tissue samples to discover tissue from areas of the brain with little epileptic activity was lower in MAPK activity with an increased presence of DUSP4 protein. The next steps for these research involve searching for drugs with the potential to affect these pathways. Dr Loeb is currently optimistic about the team’s efforts:

These DUSP4-targeting drugs would represent a new kind of ‘disease-modifying’ treatment for epilepsy, which currently does not exist,”

 If the team are successful in their efforts, this therapeutic will have the potential to alter the disease mechanism itself hence changing the way epilepsy is treated. However, current drugs used for this purpose are intended for treating some cancers, reported to also entail severe side-effects. Therefore, further research is crucial in developing a treatment with fewer side-effects suited for therapeutic use in the brain.

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