Conclusions
The evidences and examples discussed in previous sections clearly indicates that identifying the pathogenic variant in individual patients with genetic epilepsies is relevant not only for diagnosis and prognosis, but also for patient’s management including selection of the best medication and/or the indication of which drugs might worsen seizure frequency or cause severe side effects thus should be avoided. Research is now very sensitive to the urgent need to identify a cure for the disorder/diseases improving seizures and accompanying comorbidities.
Furthermore, our increased understanding of the aetiologies of epilepsies, in some patients, allowed to identify specific targets for therapies that go beyond ASM and that enable treatment of the cause of epilepsy. We are already witnessing a major shift in our paradigm of epilepsy treatment and have moved towards the era of therapies that target the underlying cause and mechanisms of epilepsy. Available, commercialised and approved by the authorities, aetiology-based treatments are only partially satisfying, several drugs have proven effective in some patients and not in others carrying similar genotypes. Results are discordant and not univocal for most of the newly proposed, precision medicines. Moreover such treatments are still focused on stopping seizures.
There is no doubt that gene therapy will change our therapeutic approach to monogenic epilepsies. To reverse the pathophysiological impact of pathogenic variants, gene editing seems to be a very promising tool and is likely to be most effective when administered during the early stages of disease or even preventively. In this scenario, the challenge for epileptologists is to identify the causes of epilepsy early in order to promote preventive therapies and to avoid the occurrence of epilepsy, including seizures and comorbidities.
In conclusion the whole scientific community is rapidly evolving towards a more curative, pathophysiology-based and preventive therapeutic approach of disorders featuring seizures and comorbidities. Meanwhile, there are three main requirements for a systematic approach to precision medicine in epilepsy: first of all is patient’s registry, a key requirement to enrol large cohorts of individuals with epilepsy who have been phenotypically and genomically characterized; second a standardized functional characterization of mutations in each of the epilepsy genes and third, since we are dealing with rare disorders, multi-center, randomized, controlled trials are needed and feasible when functional studies identifies new targets that might be translated into personalized and tailored drugs. Reaching these goals depends on the development of collaborative and integrated research groups that bring together researchers with clinical, genetic, and biological expertise. Physicians and families are ready and looking forward to this new era of precision medicine.
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