Treatment of Epilepsy with Plinabulin or Halimade or Diketopiperazine derivatives

Epilepsy is among the most common severe neurological conditions, affecting more than 70 million people worldwide [Sander (2003) Curr Opin Neurol 16, 165-170; Ngugi (2010) Epilepsia 51, 883-890; Singh & Trevick (2016), Neurol Clin 34, 837-847. It is characterized by an enduring predisposition of the brain to generate epileptic seizures, with neurobiologic, cognitive, psychological, and social consequences [Fisher et al. (2005) Epilepsia 46, 470-472]. The treatment of epilepsy consists mostly of pharmacotherapy with antiseizure drugs (ASDs) to control seizures [Golyala & Kwan (2017) Seizure 44, 147-156.]. Despite considerable efforts, current ASDs fail to control the seizures of 30% of patients due to drug-resistance [Dalic & Cook (2016) Neuropsychiatr Dis Treat 12, 2605-2616.]. Uncontrolled epilepsy can result in a poorer quality of life because of physical, psychological, cognitive, social, and occupational problems [Golyala & Kwan (2017) cited above; Blond et al. (2016) Neurol Clin 34, 395-410, viii.]. Moreover, first-line ASDs are associated with important adverse effects that can significantly impact daily life and are a main cause of treatment failure [Dalic & Cook (2016) cited above Neuropsychiatr Dis Treat 12, 2605-2616; Moshe et al. (2015) Lancet 385, 884-898; Cramer et al. (2010) Expert Rev Neurother 10, 885-891]. Hence, there is a high need for the development of safer ASDs that are more effective against drug-resistant seizures.

WO2008103916 discloses combinations therapies for cancer and neurogical disorders, wherein panaxytriol and a variety of tubulin binding agents are disclosed.

Zebrafish animal models for screening compounds for anti-epileptic activity have been described [e.g. MacRae and Peterson (2015) Nat Rev Drug Discov 14, 721-731].