Weekly Roundup – 18th October – New hope for CDKL5 Disorder?

Hello and welcome to the Epilepsy in English weekly roundup – a new section offering rapid-fire plain English explanations of a few highlights in epilepsy research over the last seven days.

New hope for treatment of developmental deficits in CDKL5 deficiency disorder?

CDKL5 Deficiency Disorder (or CDD for short) is an epilepsy syndrome which affects children (mainly girls) from the first few weeks of life. It happens in 1 out of 42,000 births, making it one of the most common genetic causes of epilepsy. CDD causes drug-resistant seizures, problems with brain development, intellectual disability and reduced muscle tone.

We still don’t have a clear picture how CDD actually leads to these symptoms and we still don’t have many treatment options. This study used genetic tricks to restore CDKL5 in mouse models of the disorder. They showed that, by re-adding CDKL5 to the brain, they could reverse behavioural changes in the affected mice. The researchers also corrected specific electrical problems in brain cells, caused by CDD.

The study presents hope of new treatment strategies for a devastating disorder and, excitingly, the approach could be successful even after CDD has begun, possibly reversing some of the symptoms. However, the study was only performed so far in male mice. More investigation is needed to see if the treatment works in females and, of course, in humans.

Temporal manipulation of Cdkl5 reveals essential postdevelopmental functions and reversible CDKL5 deficiency disorder–related deficits – Journal of Clinical Investigation – 15th October

Can perampenal be used to stop seizures in focal cortical dysplasia?

Focal cortical dysplasia (or FCD, because we scientists love a good acronym) is strongly associated with drug-resistant seizures. It happens when the cells within a specific part of the brain become malformed. Since FCD is limited to a small and well-defined part of the brain, one of the most effective current treatments options is to surgically remove the affected brain tissue. However, depending on the exact location of FCD, this might not be possible because the side effects would be severe.

This study obtained human brain tissue samples from people undergoing surgery for FCD. The researchers used these samples to test the effectiveness of perampenal – a clinically available anti-seizure drug – in FCD. They showed that perampenal can strongly reduce epileptic-like activity in slices of this brain tissue. This is most likely because it acts upon specific parts of brain cells which are known to be important in FCD.

The findings are very promising because they show that perampenal can reduce brain activity even in real human FCD tissue. As always, the approach needs to be tested in actual humans with FCD. However, because perampenal is already used in different types of epilepsy, we know that it is safe and this might support a faster move towards clinical trials in FCD.

The AMPA receptor antagonist perampanel suppresses epileptic activity in human focal cortical dysplasia – Epilepsia Open – 15th October

And finally – A new gene linked to neurodevelopmental disorders and epilepsy

Last but not least, researchers confirmed a new gene mutation that can cause epilepsy. GABRD is a gene that has previously been associated with epilepsy, but it wasn’t clear how relevant it might be in humans. This study reported cases of epilepsy, and neurodevelopmental disorders, caused by mutations to GABRD. Depending on the exact nature of the gene mutation, it can either cause GABRD to be more or less active, with the exact disease symptoms depending on this.

Gain-of-function variants in GABRD reveal a novel pathway for neurodevelopmental disorders and epilepsy – Brain – 11th October

Written by Gareth Morris – Monday 18th October

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