Diseases of the central nervous system

Nervous system diseases, such as Alzheimer’s and other neurodegenerative disorders, chronic pain, and epilepsy, represent a serious therapeutic problem with a substantial social and economic impact on the whole of society, particularly due to the prevalence of these diseases in older age groups. At present, there are very limited treatment options for these conditions, and they are usually accompanied with a number of adverse side effects. There is an unmet medical need for the development of new drugs to treat these diseases that requires investigation of the underlying mechanisms. Recent research has pointed to the significance of various signaling molecules, neuronal membrane receptors, and the relationship between neural regulation and the development of various metabolic pathological conditions. An important related pathological phenomenon is neuroinflammation, i.e. inflammatory changes in the peripheral and central nervous systems. Neuroinflammation is also implicated in the development of several metabolic disorders. 

What we’re working on and what we’ve accomplished

The goal of the collaboration between IOCB, IPHYS, and IKEM is research of the mechanisms behind the development of nervous system diseases and the rational design and preclinical testing of new potential drugs. Currently, our strategy is based primarily on the development and modification of substances known as neurosteroids, which form within the body and can substantially influence the function of various receptors. At the same time, in collaboration with IKEM, we are planning studies focusing on the role played by neuroinflammation. 

A significant factor in the development of many serious neurological and psychiatric disorders, such as acute or chronic neurodegeneration, Alzheimer’s disease, autism, schizophrenia, and epilepsy, are pathological changes in the function of glutamate N-methyl-D-aspartate (NMDA) receptors. The goal of research led by Prof. Ladislav Vyklický (IPHYS) and Dr. Eva Kudová (IOCB) is to discover substances that can modify excessive increases or decreases in the function of these receptors. Results obtained from animal models have shown that the neurosteroid derivatives we are developing have a significant effect in preclinical studies. 

Epilepsy is characterized by more than 25 syndromes and numerous types of seizures, which can vary both in terms of severity and therapeutic response. A group headed by Prof. Pavel Mareš (IPHYS) and Dr. Eva Kudová (IOCB) has demonstrated that in model experiments on animals, neurosteroids can decrease seizure frequency, mortality, and cell death while also reducing anxiety without impairment of learning and memory. 

Collaboration on these projects has resulted in multiple of publications in prestigious journals, patents, and promising substances prepared for preclinical testing. 

Recently, research has begun in the treatment of neuropathic pain, which has many causes, frequently traumatic damage to peripheral nerves and the brain, or results from diabetes, viral diseases, or tumors and their treatment with cytostatics. A substantial role in the development of neuropathic pain is also played by neuroinflammation. Treating neuropathic pain is difficult. It can lead to drug addiction and is often entirely ineffective. The goal of research projects headed by Dr. Jiří Paleček and Dr. Jan Jakubík (IPHYS) and Dr. Eva Kudová (IOCB) is to develop new neurosteroids with enhanced analgesic properties and without major side effects that could serve as potential pain medications.