A new small molecule that can be taken orally, called ADX71149, could have antiepileptic effects on its own or when used in combination with the widely available anti-seizure drug levetiracetam according to experiments conducted in a mouse model of epilepsy, the results of which were published in the scientific journal Epilepsia.Robert Lütjens, Head of Discovery of Addex Therapeutics that co-developed ADX71149, said in a press release: “These studies performed by our collaborator Janssen Pharmaceuticals, Inc. suggest there is a positive pharmacodynamic relationship or strong synergistic effect for ADX71149 and levetiracetam when given in combination”. He added that if this effect can be translated into the clinic, it could offer a potential treatment option for people with epilepsy.ADX71149 is a molecule that binds to a receptor called metabotropic glutamate receptor 2 or mGluR2, which is involved in most aspects of normal brain function.  In order to test the efficacy of the compound, researchers led Professor Steve White at the University of Utah used an approach called the 6 Hz psychomotor seizure test. The test assesses the ability of new compounds to block a psychomotor seizure, which is induced by long-duration, low frequency (6 Hz) stimulation, a model of therapy-resistant complex partial seizures.The results showed that ADX71149 is able to reduce seizures on its own and in combination with LEV. Importantly, the use of ADX71149 enables the reduction of the dose of levetiracetam necessary to obtain a full response. This is important because high doses of levetiracetam are associated with adverse side effects, such as aggression, nervousness, anxiety, somnolence, and fatigue, which limits its use.When scientists used a fixed dose of ADX71149, they saw that the effect of levetiracetam was increased almost 35 fold. When they kept the dose of levetiracetam constant and used different doses of ADX71149, they found that the efficacy of ADX71149 was increased 14 fold. These results suggest that ADX71149 and levetiracetam increase each others efficacy and a combination of the two compounds could potentially be a therapeutic option for people with drug-resistant epilepsy.“Treatment-resistant epilepsy remains a high unmet medical need, with new avenues of treatment urgently needed,” said Tim Dyer, the chief executive officer of Addex Therapeutics. “We are continuing to explore with Janssen how best to move ADX71149 into a Phase 2a proof of concept study,”Author: Dr Özge Özkaya