Adenosine is a molecule naturally present within our body that can suppress overactivity of neurons. During an epileptic seizure, the adenosine levels in the brain will rise thereby helping to suppress the seizure. Adenosine acts by binding to specific receptors on neurons, being the adenosine receptors. One of the most important receptors in this category for seizure suppression is the A1-receptor.
Even though adenosine provides a natural protection mechanism, it is hard to use this molecule in the treatment of epilepsy. This is mainly because adenosine binds to all adenosine receptors in the body which can cause side effects. To prevent this, our lab researches a molecule called CPA (N6-cyclopentyladenosine), which is a chemical variant of adenosine that specifically binds to A1-receptors. Previous studies have shown that CPA is effective in suppressing seizures, but can also have side effects. This is because it binds on all A1-receptors spread throughout the body. That is why we focus on the innovative solution of photopharmacology.
With photopharmacology, we can activate the CPA molecule only in the region where it is needed by applying light. A photoreactive form of CPA was developed, named photocaged CPA (pcCPA). In this form, CPA is bound to a photoreactive cage, prohibiting the binding of CPA to the A1-receptors. When pcCPA is exposed to light in a specific region of the brain, the photoreactive cage will detach from the CPA molecule. This reaction activates CPA and results in the binding of CPA to its receptor and the possibility to exert its function specifically in this specific location. For epilepsy research, we target the location where the seizures originate with the aim to suppress the seizures.
This research is done in an epilepsy mouse model to test the efficacy of this therapeutic method. The brain activity and amount of epileptic seizures is measured through EEG measurements. After injection of pcCPA and local illumination, the results showed a significant decrease of seizures during illumination. Besides researching the effectiveness, also the possible side effects were assessed using a rotarod. The results showed that the use of pcCPA and illumination is also safe compared to CPA only.
