New drug candidates for treatment of neuropathic pain and epilepsy.

Summary of the technology

Despite the large number of available antiepileptic drugs, approximately 30% of patients fail to control seizures, and among those experiencing partial seizures (simple, complex, and secondarily generalized) the percentage is even higher at around 40%. Such a form of epilepsy is called drug resistance. One reason for the wide prevalence is the problem of insufficient efficacy of the currently available antiepileptic drugs. Also neuropathic pain in many cases is unable to control with use of currently used drugs. One of the possible reasons is that there are many mechanisms for the formation of the peripheral and central neuropathic pain, which frequently are still poorly known. Neuropathic pain is a serious clinical problem which affects up to 7 ‐ 8% of the population. Compounds included in the offer meet requirements for new, innovative drugs efficient in epilepsy and neuropathic pain cases which are still unmet medical needs (particularly drug resistant epilepsy and uncontrolled neuropathic pain – frequently of unknown etiology).

Description of the technology

The subject of this in-licensing offer is a number of drug candidates for treatment of epilepsy and/or neuropathic pain. The group of 80 molecules, containing two in late preclinical phase, have been developed by at the Jagiellonian University Medical College. The two most active molecules have been tested in an array of pre-clinical assays; their efficacy has been evaluated and confirmed in vivo. Tested compounds are effective in drug resistant refractory epilepsy and neuropathic pain of various etiology.

Specifications

The key features of the offered compounds are: • small molecules, • sodium channel blockers, • complete physicochemical analyses performed, • well described solubility and stability – the compounds fulfill the Lipinski rule of five, • enantiomers differentiated by pharmacodynamics, • broad spectrum of efficacy in both epilepsy and neuropathic pain models – exceeding currently available antiepileptic drugs (AEDs), • efficacy in focal seizures and pharmacoresistant seizures exceeding other AEDs, • long duration of activity, • extensively tested in vitro, ex vivo and in vivo for other possible mechanisms of action, • well tested for possible side effects: • shown broad safety, no mutagenicity, minimal CYP influence. Several molecules underwent proof of concept studies within the Antiepileptic Drug Development program at the National Institute of Neurological Disorders and Stroke (part of the U.S. National Institutes of Health). To date, complete proof of concept documentation for one of the selected molecules is available.

Main advantages of its use

  • Broad spectrum of efficacy in both epilepsy and neuropathic pain models – exceeding currently available antiepileptic drugs (AEDs): efficacy also in drug resistant, refractory epilepsy.
  • Efficacy in focal seizures and pharmacoresistant seizures exceeding other AEDs.
  • Extensively tested in vitro, ex vivo and in vivo for other possible mechanisms of action.
  • Long duration of activity.
  • Shown broad safety, no mutagenicity, minimal CYP influence.
  • Well described synthesis method that guarantee high purity and stability of compounds.
  • Well tested for possible side effects.

Applications

  • Due to unmeet medical needs and high number of patients suffered from epilepsy and neuropathic pain numerous research projects are conducted in this area of science.
  • Potential entities interested in this technology are pharmaceutical companies focused on nervous system diseases.
  • The most promising applications of the invention are neuropathic pain of various etiology and drug resistant and refractory epilepsy.

Related Keywords

  • Pharmaceutical Products / Drugs
  • Neurology, Brain Research
  • Medical Research
  • Genetic Engineering / Molecular Biology
  • Medical Health related
  • neuropathic pain
  • antiepileptic drugs
  • drug candidates
  • epilepsy
  • neurological disorders
  • Neurological
  • neurology
  • neurologist
  • nervous system

About Jagiellonian University

Jagiellonian University, founded 1364, is the oldest university in Poland and one of the oldest worldwide. The research and teaching activities are conducted at 15 faculties, including the Medical College (Collegium Medicum). Over 3,700 researchers work at the university and the total number of students is about 50,000.

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