James Hopkins, PharmD

ICE the Inferno

As many as 40% of children with epilepsy do not find seizure freedom with anti-epileptic drug therapy and are considered “refractory” , “intractable“, or “drug resistant” patients. An astounding 70% of patients suffering from epilepsy do not know what is causing their seizures, and the cause is determined as “idiopathic” or “cryptogenic” . The definition of “drug resistant” epilepsy as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. Drug resistant epilepsy in children can lead to brain damage, developmental delays, psychological abnormalities, and even death.

The Intractable Childhood Epilepsy Alliance (also known as the Ion Channel Epilepsy Alliance) is committed to facilitating the understanding of the root cause of the epilepsies and avenues to better treatment and ultimately a cure. ICE was founded by Harriet Davies, PharmD after her daughter, Lilly, was diagnosed with Dravet syndrome. Dravet syndrome is an epilepsy syndrome that is caused by a mutation in the SCN1A gene in the brain. The SCN1A gene regulates activity in one of the ion channels in the brain, the sodium channel. Harriet the unique role of a health care professional and mother of a child with a catastrophic drug resistant epilepsy. “ICE the Inferno” , the slogan ICE Alliance has adopted, reflects the devastation, grief and pain suffered by the children who experience uncontrolled and life threatening seizures as well as the families who love and take care of these children while epilepsy destroys their developmental abilities and often takes their lives.

See also  Professional Advisory Board

Ion channels provide the basis for the regulation of excitability in the central nervous system and in other excitable tissues such as skeletal and heart muscle. Consequently, mutations in ion channel encoding genes are found in a variety of inherited diseases associated with hyper- or hypo-excitability of the affected tissue, the so-called ‘channelopathies.’ Genetic defects (mutations) in ion channels are associated with several forms of human idiopathic epilepsies. To date, 12 mutated genes have been identified. They code for Na(+) (SNC1A, SNC2A, SNC1B), K(+) (KCNA1, KCNQ2, KCNQ3) and Cl(-) (CLCN2) channel subunits, as well as neurotransmitter receptor subunits including Cl(-) channel GABAA receptor (GABRA1, GABRG2) and cationic channel acetylcholine receptor (CHRNA4, CHRNB2). One ion transporter Na(+)/K(+) ATPase gene (ATP1A2) has also been identified. The epilepsy syndromes related to these genes are as diverse as benign familial neonatal (BFNC – KCNQ2 and 3) and infantile (BFNIC – SNC2A and ATP1A2) convulsions, episodic ataxia with seizures (AE2 – KCNA1), generalized epilepsy with febrile seizure plus (GEFS+ – SCN2A, 1A, 1B and GABRG2), autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE – CHRNA4 and B2), severe myoclonic epilepsy of infancy (SMEI – SNC1A), juvenile myoclonic epilepsy (JME – GABRA1 and CLCN2), and childhood and juvenile absence epilepsy (CAE, JAE – SNC1B, GABRG2 and CLCN2). Despite the difficulty to correlate the gene mutation to the clinical outcome (genotype to phenotype), these studies have increased our understanding of causal mechanisms of epilepsy and open a wide range of possibilities for developing better antiepileptic drugs and treatments. The knowledge of the role of the ion channels in the epilepsies is allowing the design of new and more specific therapeutic strategies. Many of the genes that have been implicated in idiopathic epilepsies code for ion channels, whereas syndromes with epilepsy as a main feature are caused by genes that are involved in functions as diverse as cortical development, mitochondrial function and cell metabolism. Each ‘epilepsy gene’ that is identified provides new and fascinating insights into the molecular basis of neuronal excitability and brain function.

See also  ICE Statement

Please utilize the website to learn about the intractable childhood epilepsies and consider supporting our cause as we fight the battle with uncontrolled seizures.

ICE is a voluntary non-profit with no paid employees. The contents of this website have been written by Harriet Davies, PharmD or Doctor of Pharmacy students under her direction through an ICE Drug Information rotation with accredited pharmacy schools in North Carolina. Additionally, other interns or professional volunteers contribute to the website from time to time.

All donations made to ICE Alliance go to support education or research initiatives.