Genetic medicine to treat epilepsy

The word “Idiopathic” is one of the most used in medicine. Maybe the reader heard it or ever read it in a medical report. And it is paradoxical, because idiopathic means that we do not know the origin or cause of a health problem. Idiopathic diseases, then, are those in which the doctor does not know why they appeared. And this has happened in over 70% of cases of epilepsy until very recently. Fortunately, something has changed in recent years.

Epilepsy it is a neurological disease that almost affects 1 in 100 people, so it is calculated that they are around Half a million people with epilepsy In Spain. It occurs at all ages, although it is more common in those ages when the brain is subject to several changes and evolutions, such as in children (due to neurodevelopment) or the elderly (due to neurodegeneration).


People with epilepsy, by definition, have a predisposition to seizures, which can manifest in different ways:

– A generalized seizure loss of consciousness (which most people identify as seizures)

But also with more subtle symptoms such as:

Trembling on one arm

– A disconnecting from the environment with the loss of reaction to the environment (absence) or all sorts of subjective perceptions (from an exaggerated feeling of “déjà vu” to the appearance of hallucinations in vision). He also suffers from other problems, such as:

– A social stigma classic that persists today

– Difficulties in the work environment

Impossibility to drive vehicles if seizures are not controlled. And this is a key issue, crisis control. Today, with modern antiepileptic treatments, a large majority of people with epilepsy have controlled seizures and can lead a normal life in all respects.

Common treatment

However, in about a third of people with epilepsy, is refractory to drugs. That is, for many medications that the patient takes (there are nowadays more than 20 available on market), epileptic seizures continue to occur. And here comes the need (and possibility) of precision medicine.

Epilepsies were treated classic in the same way, regardless of the cause, but in recent years we have seen that different causes require different treatment strategies. For many focal epilepsy, which depend on a lesion (focus) in a part of the brain that generates epileptic seizures, performing a correct study with neuroimaging techniques and state-of-the-art electroencephalogram allows epilepsy surgery (removal of the area of ​​the brain that generates epilepsy) and eliminate seizures . And now more and more with “minimally invasive” operations, such as those we perform in specialized centers for laser epilepsy or thermocoagulation. For others, they have a immunological origin (inflammatory, so fashionable in these COVID-19 times), treatments will need to be immunomodulatory.

Genetic treatment

The big leap in quality In recent years it has been about genetics. Genetic diagnostic techniques put an end to the concept of “idiopathic” or “without known cause” in the worst epilepsies, those that affect children and are associated with intellectual disabilities, autism and other neurodevelopmental problems.

Currently, with modern sequencing techniques, we are able to diagnose up to 50% of those previously considered “idiopathic”, reducing uncertainty, seeking answers and anxiety about not having a diagnosis.

Parents of children with epileptic encephalopathies or neurodevelopmental problems (this is how this type of severe epilepsy is classified) suffer from what has been called the “diagnostic odyssey”: a tireless search for answers that becomes a hard and winding path. But the genetic diagnosis not only failed to avoid the diagnostic odyssey. It also allowed the performance of precision drugs in several cases. Be aware that if there is a mutation in SCN1A (the most common mutant gene in epilepsy), some medications cannot be used because the person will get worse or other specific medications must be used because they help more.

And the barrier of precision medicines continues to grow. Rare diseases, classically “orphans” in research and treatment, are now receiving increased attention, and clinical trials with specific therapies are multiplying. For example, with cannabidiol or CBD (a cannabis derivative) or fenfluramine in Dravet syndrome or with ganaxolone in CDKL5 deficiency syndrome, to name a few examples from our team’s clinical trials.

A comprehensive vision, with specific therapies, avoiding harmful ones and paying attention to other aspects of the disease, such as cognitive, social or movement problems, are essential to help these people and their families. Moreover, in the current context, in which the COVID-19 pandemic has reduced the access of these families to the necessary care and treatment resources. However, the path of precision medicine is unstoppable, and in the coming years many more diagnoses and personalized therapies will come.

We are talking about Dr. Ángel Aledo Serrano, a neurologist specializing in epilepsy at the Corachan Clinic


Twitter: @Aaledo