Projects

IOCB Tech’s main responsibilities include identifying commercially attractive projects developed within the IOCB, followed by analyzing their market potential and patentability, protecting their intellectual property, supporting the given projects’ development in the form of project management, finding commercial partners, and negotiating the contractual terms for signing license agreements.

We have participated in the negotiating and concluding of more than a dozen key license agreements with important pharmaceutical partners including Gilead Sciences, Merck, Novo Nordisk, and SHINE Technologies.

Our main areas of interest are the development of new drugs, diagnostics, and research tools. Our current portfolio includes projects focusing on a variety of therapeutic areas: e.g., the central nervous system, inflammation, cancer, and microbial resistance, as well as separation methods and research tools.

Neurosteroids for the treatment of epilepsy Active

Scientists:
Scientists: Principal Investigator: Eva Kudová (IOCB Prague). Team IOCB Prague: Hana Chodounská, Ewa Szczurowska. Team IPHYS: Hana Kubová, Pavel Mareš

Challenge

Epilepsy is an umbrella term covering a wide range of syndromes and conditions which manifest with seizures. Pharmacoresistant (refractory) epilepsy is defined as failure to achieve seizure freedom following adequate trials of two tolerated and appropriately chosen antiepileptic drugs. Among epilepsy patients, 30% or more are considered pharmacoresistant. Pharmacoresistant epilepsy can have a devastating effect on the patient’s quality of life and is associated with an increased risk of sudden unexpected death.

Technology

Neuroactive steroids are steroidal compounds known to regulate brain excitability through interaction with ligand- and voltage-gated ion channels, as well as GPCRs. We have synthetized novel neurosteroids which show potent anticonvulsant effects in multiple animal models of seizures, including models of pharmacoresistance. The presumed mechanism of action for our lead compound is allosteric modulation of GABAA receptors.

Anticonvulsant efficacy of our lead compound (Compound 1) has been demonstrated in the following animal models:

Pentylenetetrazole (PTZ)-induced seizures (zebrafish, Fig. 1, panel A), screening model, contracted from ZeClinics, Barcelona, Spain.
Pentylenetetrazole (PTZ)-induced seizures (rat, Fig. 1, panel B), Institute of Physiology ASCR, Prague, Czech Republic.
Pentylenetetrazole (PTZ)-induced seizures (mouse), Institute of Physiology ASCR, Prague, Czech Republic. In mice, the anticonvulsant effect in the PTZ-model was sex-dependent (observed in females only).
6 Hz Electrical Stimulation Test (rat, Fig. 1, panel C), Institute of Physiology ASCR, Prague, Czech Republic.✤
Tetramethylenedisulfotetramine (TMDT)-induced seizures (rat). In collaboration with L. Velíšek, M.D., Ph.D., and M.P. Shakarjian, Ph.D., New York Medical College, Valhalla, NY, USA.✤
Ethyl ketopentoate model (zebrafish, Fig. 1, panel A), contracted from Laboratory for Molecular Biodiscovery KU Leuven, Leuven, Belgium.✤
Lamotrigine-resistant amygdala kindling model (rat), Epilepsy Therapy Screening program (ETSP), National Institutes of Health/National Institute of Neurological Disorders and Stroke, Rockville, MD, USA (Table 1).✤

[Models marked with ✤ are reported to be pharmacoresistant.]