Over 80 million people suffer from epilepsy and Alzheimer's worldwide.
If they were a country, it would be around the 35th largest by population in the world, larger than Canada. These numbers are expected to increase dramatically, with estimates ranging from 65 million by 2030 to 115 million by 2050. The suffering is not limited to the patients, as their families, loved ones and caregivers are also put under great emotional and physical burdens.
Alzheimer’s and Epilepsy: Exploring the common cause to treat both diseases.
We are developing a way to disrupt the vicious cycle of energy deficit and hypometabolism, that will allow to prevent, stop and reverse Alzheimer’s (AD), acquired epilepsy (AE) - and hopefully other neurodegenerative diseases. The focus of our research is the pathology of energy metabolism in the brain and its effect on the diseases. In our most recent studies, we demonstrate that there is a way to correct these pathologies and stop the progression of both diseases.
Our working hypothesis states that a combinatorial treatment leading to both the increase in cellular antioxidant defense and the decrease of ROS production will result in preserving brain glucose metabolism and preventing the initiation and progression of AD and AE pathogenesis. The main goal of the project proposal will be to verify the molecular mechanism(s) of reduced glucose utilization and based on uncovered targets, using animal models, to develop the potentially efficient treatment for preventing both AD and AE.
The candidates
We paid specific attention to the molecule called NOX, which usually is passive, but when activated, generates superoxide. It is an essential part of the immune response. However, it can also result in glucose hypometabolism and therefore is potentially responsible for disease initiation and progression.
Preliminary results
We demonstrated that inhibition of a form of NOX, NOX2, prevents one of the amyloid-beta peptides from damaging glucose metabolism and glycolysis in brain slices 7. Besides, NOX activation underlies both seizure onset 8 and likely the seizure-induced decrease in glucose utilization in brain slices 9. Importantly, in vivo, inhibition of brain glucose utilization initiates epileptogenesis 10, triggering a vicious cycle scenario of epilepsy progression 1.