We previously found that genetic mutants with reduced expression or activity of Scn8a are resistant to induced seizures and that co-segregation of a mutant Scn8a allele can increase survival and seizure resistance of Scn1a mutant mice. In contrast, Scn8a expression is increased in the hippocampus following status epilepticus and amygdala kindling. These findings point to Scn8a as a promising therapeutic target for epilepsy and raise the possibility that aberrant overexpression of Scn8a in limbic structures may contribute to some epilepsies, including temporal lobe epilepsy.

Using a small-hairpin-interfering RNA directed against the Scn8a gene, we selectively reduced Scn8a expression in the hippocampus of the intrahippocampal kainic acid (KA) mouse model of mesial temporal lobe epilepsy. We found that Scn8a knockdown prevented the development of spontaneous seizures in 9/10 mice, ameliorated KA-induced hyperactivity, and reduced reactive gliosis.

These results support the potential of selectively targeting Scn8a for the treatment of refractory epilepsy.

According to the study, “Interactions between GHRH and GABAARs in the brains of patients with epilepsy and in animal models of epilepsy” [1]:

According to a study from Bethany E. Hosford et al., “Ablation of peri-insult generated granule cells after epilepsy onset halts disease progression,” [1]:

This study is an open label, adjunctive, proof of concept, pilot clinical trial. Pediatric patients with epilepsy and clinically significant anxiety will be recruited and if enrolled will receive active treatment, involving flexible dose titration of clobazam and will be monitored for a period of four months. The study will be monitored and overseen by the Johns Hopkins Hospital Institutional Review Board.

Eligibility Criteria

Ages Eligible for Study: 6 Years to 17 Years (Child)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No

Inclusion Criteria:

• Established diagnosis of epilepsy, characterized by focal seizures with suspected or documented localization in the temporal lobe. All participants will have active epilepsy that requires treatment with anticonvulsant medication.
  • Although it is not necessary to be seizure free, a seizure baseline period will be established in the 60 days prior to enrollment into the study.
  • Current regimen of anticonvulsant drugs must have been stable for 30 days prior to entry into the study.
• No episodes of seizure clusters of status epilepticus within 30 days prior to entry into the study.
• Established symptoms of anxiety with functional impairment.
• Baseline behavioral criteria for inclusion will include subscale scores above the norm for age and gender on one of the following:
  • Pediatric Anxiety Rating Scale (PARS).
  • Multidimensional Anxiety Scale (MASC)
• Male or female participants equal to or above age 6 and below age 18 at the start of the study. No exclusion will be made on the basis of gender or minority status.
• Good general health as determined by medical history and physical examination.
• Ability to swallow pills (participant will receive pill swallowing instruction if necessary). The medicine may be cut into pieces and/or mixed with applesauce.
• If female of childbearing age, a negative urine or serum pregnancy test must be established or assured at baseline. Additionally, the participant must agree to use abstinence or appropriate contraception methods or be otherwise incapable of pregnancy for the duration of the study. Pregnancy test results will be shared with parent or guardian. Pregnancy status (or prevention) and abstinence or contraception methods will be addressed throughout the study for females of childbearing age as well as for post-pubertal males.
• Previous subjects who failed at any point to meet continuation criteria and withdrew early may be considered for re-enrollment by the PI on a case-by-case basis.
• Participant or legal caregiver capable of providing informed consent and fully capable of monitoring the subject’s disease process and compliance with treatment.

Exclusion Criteria:

• Previous allergic or hypersensitivity reactions to Onfi® or benzodiazepines
• Active substance abuse or dependence within 30 days of enrollment
• DSM-V diagnosis of psychotic illness or imminent risk of harm to self or others.
• Current use of antidepressants
• Current standing use of benzodiazepines (except as “rescue” medicine)
• Serious or unstable medical or neurologic conditions such as HIV, liver or kidney disease, cancer or diabetes.
• Participation in a previous experimental drug study within 30 days of baseline visit.
• Estimated IQ<70 as indicated by initial clinical assessment (rendering rating scales invalid)
• Insufficient capacity of caregiver or legal guardian to understand and appropriately consent for study procedures

The authors performed a retrospective analysis utilizing Medicaid claims to measure the efficacy of vagus nerve stimulation therapy. Thirteen pediatric patients were studied. After vagus nerve stimulation implantation, the patients experienced fewer unplanned inpatient visits.

A Sleep study, “1145 Long-Term Seizure Control in Epileptic Patients with Obstructive Sleep Apnea Using Positive Airway Pressure Therapy” found [1]:

The study “Low-dose fenfluramine significantly reduces seizure frequency in Dravet syndrome: a prospective study of a new cohort of patients” found [1]: