Team of experts led by Scott C. Baraban, professor of neurological surgery from University of California San Francisco is excited by their recent discovery that holds a significant potential for treating a rare genetic form of epilepsy in children.
The epilepsy drug targets were identified in experiment carried out on zebrafish which later went for a small clinical trial that involved children suffering from Dravet syndrome, a rare form of childhood epilepsy.
The study finding was explained in the university press release on 3th March, which was also published in Brain-A Journal of Neurology.
This study is unprecedented in its approach as it initially observed the drug efficacy of various drugs on zebrafish which were engineered to carry the mutated gene with corresponding effects of Dravet syndrome in children.
Back in year 2013, the experts at UCSF found that a drug named ‘clemizole’ helped to reduce seizures in zebrafish which were carrying gene mutation for Dravet syndrome. Upon reaching this finding, the team could not find a clear link between this anti-histamine drug (usually primarily to treat allergies) and its anti-epileptic effects.
To find a logically sound reason for the effect of clemizole, they studied the effects of several anti-histamines on zebrafish which failed to show an anti-epileptic activity. This signified that the anti-histamine properties were not behind the anti-epileptic activity of the drug, but the underlying role of clemizole as neurotransmitter helped in treating epilepsy. Further investigation showed that, clemizole worked on the serotonin receptors that help in regulating nerve impulses and subsequently reducing seizure frequency.
Despite, the encouraging results with the use of clemizole, the researchers could not continue with the research as FDA had restricted the use of clemizole in clinical-grade formation. This led them to look for other FD approved drugs which can work as ‘serotanin-receptors’ like clemizole.
As a result of this, a weight-loss medication known as ‘lorcaserin’ was found to have anti-epileptic effect in zebrafish larvae. After receiving positive results from fish model, the drug’s efficacy was observed in a clinical trial that recruited five patients of Dravet syndrome, who were aged between 7 to 18 years.
In one patient, the seizures were not observed for three weeks, in other patient seizures were not observed for two weeks and other participants showed a significant reduction in seizure frequency after the drug was administered.
Now, the team is working on finding and engineering anti-epileptic drugs by making use of zebrafish model which helps them screen over 100 drugs per month.
Vicky Whittermore, Ph.D., program director at the National Institute of Neurological Disorders and Stroke was thrilled with the findings of the study and said, “This is the first time that scientists have taken a potential therapy discovered in a fish model directly into people in a clinical trial.”
He added that the findings of this study open an avenue for studying other neurological diseases in animal model for finding improved treatment modalities.
Dravet Syndrome- What We Know About This Rare Form Of Epilepsy?
Dravet syndrome is caused in children who are as young as 1 year old which is characterized by repetitive and prolonged convulsions. The condition occurs in children who carry a genetic mutation in a gene called SCN1A which is responsible for regulating the function of sodium ion channels in the brain cells. As the ion uptake in the neural cells are disrupted, high intensity impulses crossing through synapsis lead to epileptic seizures.
Interestingly, the gene mutation is not inherited by the parents but it is present as a ‘new’ or spontaneous mutation in in the genetic makeup of the infant. Due to experiencing these seizures, the children who suffer from Dravet syndrome often have severe cognitive development issues, sleep disturbance, behaviors exhibiting anxiety, delayed motor and language development.
The seizures experienced during the first year of age are often characterized as tonic-clonic seizures which are usually accompanied by fever. In this stratification of seizures, the fit takes place in two phases, namely ‘tonic’ and clonic’, as suggested by the name.
In the tonic phase, all the muscles experience stiffness, air passes forcefully through the vocal cords to produce a groaning sound which is followed by fainting. During this time, the person is likely to lose balance and fall on the floor. Due to uncontrolled movement, the cheeks or tongue are prone to be bitten and the face can also turn blue due to low blood oxygen levels.
Following this, clonic phase takes place which is associated with jerking of limbs. As the jerking stops, the muscles begin to relax and a person regains consciousness. The seizure generally lasts for up to 3 minutes.
However, Dravet syndrome is not only restricted to tonic-clonic seizures but children with this condition may have myoclonic seizures, partial seizures, absence seizures, atypical seizures, atonic seizure or non-convulsive status epilepticus.
These seizures can last for about 30 minutes under certain life threatening situations. Furthermore, children with this condition can have seizures which are triggered by slight change in body temperature, while having a hot bath, during hot weather or during an infection which is followed by a fever.
These children also commonly experience photosensitive seizures which are stimulated by flashing lights or other photic triggers.
Timely diagnosis and treatment is crucial for mitigating the condition and lowering the seizure frequently. Till date, combinations of drugs are prescribed to check drug efficacy against all types of seizures experienced. Often, this pediatric form of epilepsy remains resistant to commonly used anti-epileptic drugs that warranted a need to delve deeper into the disease and finding a therapeutic solution.
With this emerging study, it is hoped that a specific and highly effective treatment for Dravet syndrome will soon hit the pharmacies.