Conclusion
Neurochemical agents, electrical stimulation protocols, thermal or hypoxic insults, traumatic traumas, optogenetics, and rodent strains with idiopathic or audiogenic-induced seizures are only a few of the techniques used in animal models of epilepsy. Figure 1 summarises the key characteristics, applications, and limitations of the models examined here. In the last 20 years, many experimental compounds have been tested in animal models to find novel, third-generation ASMs. This has surely increased the therapeutic possibilities, especially for patients requiring a change in treatment. But the effectiveness of these new ASMs for treating newly diagnosed epilepsy is, at best, comparable to that of older ASMs.
In biomedical research, the search for appropriate animal models is a critical aspect of various clinical conditions, such as the pursuit of novel treatments for seizures that are resistant to current medications. Unlike a one-size-fits-all approach, the principle of “fit-for-purpose” guides the selection of animal models, acknowledging that there is no single ideal model for every aspect of a complex condition like autism spectrum disorder (ASD) or pharmacoresistant seizures. An essential prerequisite for advancing drug development is the availability of animal models that accurately predict therapeutic responses to drugs.
Animal models, when thoughtfully chosen, designed, and executed, constitute crucial components of translational drug development strategies. These models gain even more translational value when combined with other tools such as quantitative systems pharmacology, biomarkers, or experimental clinical trials. It is important to recognize that animal models are simplified representations of complex systems, and their purpose is not to replicate the entire complexity of a human disease but to model specific facets of the disease, such as drug-resistant partial seizures.
When employing animal models, it is imperative to have a well-defined research question and ensure that the chosen model aligns with that question. The Development of new therapies for epilepsy necessitates a close alignment between the animal model and the clinical syndrome. This alignment requires ongoing and effective collaboration between skilled clinicians and basic scientists. Besides relying on animal models, the insights and ingenuity of experienced scientists are crucial for discovering novel targets and correctly interpreting unexpected findings, potentially leading to the development of truly impactful drugs.
In this context, emerging pharmacological and gene discovery strategies offer the potential to target specific subpopulations of patients with drug-resistant epilepsy rather than searching for a universal remedy effective for all forms of intractable epilepsies.