World Epilepsy Day, interview with doctor Pasquale Striano

Doctor Striano, today is the world day against Epilepsy, which are the most important results achieved regarding this disease?

In the past twenty years huge progress was made due to the development of the techniques in molecular genetics. Besides the continuous discovery of new genes, we are getting a glimpse of important perspectives through the creation of new medical drugs, aimed at the specific pathogenetic mechanisms or with a specific action in mutated proteins, up to a gene replacement therapy in more severe cases.

In particular, similarly to what occurred in the oncology sector, the discoveries of genetics in the field of Epilepsy introduced us to the new era of the so-called ‘precision medicine’ which has as its objective offering the single patient a treatment intervening in the specific genetic defect and sometimes in the specific causative mutation of his/her form of Epilepsy.

There are various scientific publications demonstrating the effectiveness of Cannabis and its extracts in contrasting epilepsy, from your point of view, how do you value this therapeutic option?

Currently the scientific community supports the use of cannabidiol (CBD) as an adjunctive therapy to standard therapy in children and young people with rare forms of epilepsy, like the Lennox-Gastaut and Dravet Syndromes, which classically do not respond to treatments.

However, as no study has ever used CBD alone, we do not know yet if the treatment is or is not effective when other medicines turn out to be ineffective". Cannabinoids were proposed as an adjunctive treatment for epilepsy and many phase 3 clinical studies are in progress regarding the use of the molecule in paediatric resistant epilepsies and others.

Several Countries approved the use of cannabinoids for medical purposes. In our experience, many patients affected by drug-resistant epileptic disorders have had considerable benefits from cannabinoid therapy, which means reduction of the number of seizures, benefits at behavioural level and in the sleep-wake cycle, and as a consequence, improvement of the quality of life.

Commonplaces and prejudices exist towards those affected by this pathology and their relatives. Do you believe that progress has been made from the cultural point of view?

Many, still, are the prejudices, and, more in general, the cultural stereotypes which people suffering from epilepsy often have to deal with.

There are, in fact, still many people who erroneously believe epilepsy to be a rare disease or a mental disorder with scarce treatment possibilities. Also, that during a seizure one becomes violent, or that one cannot drive a car or practise sports and, when a woman is involved, that she has difficulty conceiving or that it is forbidden for her to breastfeed.

It is therefore essential, more than ever, to adopt a correct language which see to it that people affected by epilepsy are not excluded because of a condition and that they are a growing resource for the community, also at job level.

Regarding the future, in a previous interview you talked about the necessity to “implement the integrated research platforms”, where are we at the moment?

Genetic research in epilepsy represents a highly suggestive and promising research frontier at the moment. In particular, in the past few years, this has been possible through exome sequencing (exome > the protein-codifying part of the genome) of all codifying regions of the human genome (exons) in a wide group of patients, not related to each other, comparing them with the sequence of many individuals from different nationalities not affected by these pathologies.  

An example is represented by the project DISCOVER, supported by Onlus ENEA ‘heroes in research’, which has its basis on the presupposition that, in order to cure, or better to prevent, it is necessary to be aware of the genetic alterations modifying the physiological “development programme” of the cerebral cortex, and hence intervene in a targeted manner.

In fact, rehabilitation and drug therapies can, in the most optimistic scenario, mitigate the symptoms, because they are not aimed at the modification of the causes underlying the pathology. In the coming years, the systematic application of this approach to numerous rare diseases, of which the aetiology is still unknown, would allow to reveal the genetic causes and could represent an essential step towards more effective clinical management and to the development of targeted therapeutic strategies.

In Italy 500 thousand patients, “There’s a lot of work to be done”

In Italy 500.000 are the individuals affected by Epilepsy and experts estimate about 30.000 new cases, each year.
It is one of the most frequent neurological pathologies, involving all age groups, while children are the most affected. In two-thirds of the cases, in fact, the onset of the disease is before puberty”. 

“The treatment of childhood epilepsies – Carmela Bravaccio, Director of the Magazine and the website of the Italian Society of
Paediatric and Adolescent Neuropsychiatry (SINPIA) and the Polyclinic University Federico II Naples, says -  has particularly complex implications and is burdened by a wide margin of arbitrariness which has multiple origins. It is recommended, especially in the developing age and in order to improve the adherence to the treatment, that there is always adequate information on the pathology available, as well as a preference for simple therapeutic regimes, regular visits between healthcare professionals and the assisted individuals, and that personalized interventions are scheduled for the individuals in treatment and for their families/caregivers”.

“A first element of huge complexity of the treatment – the note continues – lies in the heterogeneity of the causes of epilepsies with onset in childhood and in the variety of - sometimes extremely rare - symptoms, of different severity and with often unpredictable developmental profiles. A second element of complexity results from the low specificity of the available treatments. Of the majority of the medications, in fact, the mechanism of action remain little known, often as little as the causes triggering epilepsy, while there isn’t any evidence either of the efficacy profile in relation to the specific condition to be treated. The causes of this situation result not only from the heterogeneity discussed earlier, but also from the cumbersome nature of the procedure conducting to the authorisation and the introduction on the market of molecules with anti-epileptic actions”.

“It is important to keep in mind that many cases of epilepsy are part of complex pathologies with impairment of multiple aspects of neurodevelopment which require diagnostics and care of the patient over the years and which go well beyond the treatment of the crisis, and also that this still represents the main outstanding needs of the patients and their families. Unlike other childhood neuropsychiatric disorders – Antonella Costantino, President of SINPIA, UONPIA IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico of Milan – concludes, epilepsy is covered by a good clinical network on the entire national territory, also due to the job done by scientific Societies and, and we can safely state that there are no areas in which the clinical setup is deficient with respect to the rest of Europe. A condition allowing to look at the future with hope”.