Neurological and Metabolic Diseases Research Group

Neurology

Nervous system diseases pose the greatest challenge faced by modern medicine and the healthcare system. The challenge lies, on the one hand, in the complexity of the human brain and the mechanisms which control it, and on the other hand, in treatment and social costs of nervous system diseases, which in the European Union significantly exceed the total expenditure on combating cancers, cardiovascular diseases or diabetes. Total annual medical and social costs of nervous system diseases in Europe are estimated at 798 billion euros.

The latest population projections indicate that the costs of treating nervous system diseases will increase. We must take into account the fact that societies in high- and medium-developed countries are ageing progressive (and that there is essentially no possibility to recover nerve cells in the course of human life), the stressful pace and complexity of professional and personal life of modern societies. Introducing effective therapies is among the essential elements which make it possible to mitigate the negative short-term and long-term effects of central nervous system disorders.

Celon Pharma S.A. is searching for modern and innovative solutions, trying to meet the needs of patients suffering from various kinds of nervous system disorders, including schizophrenia, dementia, Huntington's disease, depression.

Phosphodiesterase 10A inhibitors

Phosphodiesterase 10A (PDE10A) is an enzyme hydrolyzing cGMP and cAMP cyclic nucleotides which are universal cell transmitters. PDE10A is highly and specifically expressed in the striatal medium spiny neurons, making this protein an attractive target for pharmacological intervention for diseases caused by dysfunction of this part of the brain. Development of a PDE10A inhibitor can be particularly significant for patients suffering from schizophrenia and other psychoses, as well as Huntington's disease, thus offering them a chance to benefit from effective treatment without the adverse effects of metabolic therapy.

5-HT6 receptor antagonists

5-HT6 receptors are located in the central nervous system and constitute an important part of the serotonin receptors. Inhibition of 5-HT6 receptors leads to increased transduction in the glutamatergic and cholinergic system and facilitates the release of dopamine and noradrenaline. Modulation of 5-HT6 receptors, due to their location and function, may be particularly important for patients suffering from various kinds of dementias with behavioural and psychological symptoms. The objective of the project is to develop a safe, chronic therapy addressed to patients suffering from these disorders.

A new form of S-ketamine in treatment of depression

Depression is among the most common mental disorders in the world and one of the greatest challenges in treatment of this condition is drug-resistant depression. In recent years, it has been shown that ketamine, a known analgesic and anesthetic, is also a strong anti-depressant. A solution currently developed in Celon Pharma laboratories is an innovative route of administration (other than intravenous) of the active substance–S-ketamine. Such a solution will allow for a wider use of the therapy in patients suffering from depression and bipolar disorder and will significantly improve their comfort of lives.

Metabolism

New Therapies of Metabolic Diseases

Diabetes is a chronic, systemic metabolic disease characterised by elevated levels of glucose due to disordered secretion and activity of an endogenous hormone - insulin. Diabetes is one of the greatest and continually growing problems of modern medicine (WHO, 2014).

According to data published by the International Diabetes Federation (IDF), a steady increase in diabetes incidence is observed in most regions of the world. In 2014, 387 million patients suffering from diabetes were reported, of which 46.3% remained undiagnosed. IDF predicts that by 2035, there will 592 million patients globally, 80% of which will be suffering from type 2 diabetes.

It is estimated that an average of 4,9 million people every year die due to diabetes and its complications (50% of deaths occur in patients under the age of 60). There are over 56 million people suffering from diabetes, of which over 80% have type 2 diabetes (IDF, 2014). In Poland, over 2 million people have been diagnosed with diabetes, and almost 700,000 are unaware of their condition (IDF, 2014). In recent years, increased incidence of type 1 diabetes in children and adolescents has been observed in Poland. Incidence rates in the age groups: 0-4 years, 5-9 years and 10-14 years in boys are 8.7%, 13.0%, and 19.0%, respectively, while in girls they are: 7.5%, 15.5% and 14,00%. The average annual incidence growth is 9.3% and it is the highest among European countries.

It is expected that by 2030, over 10% of the Polish society will suffer from diabetes. The increased incidence of diabetes is also connected with a growing number of diabetes complications, which has a significant impact on the quality and length of life of people affected by the disease. There is a huge market demand for drugs which help manage the disease, thus impacting the length and quality of life of patients, and additionally minimise diabetes complications while ensuring good tolerability.

Research conducted by Celon Pharma focuses on two metabolic entities: obesity and type 2 diabetes.

GPCR agonists

GPCRs is a family of receptors involved i.a. in the regulation of secretion of gastrointestinal hormones and insulin. Introducing GPCR agonists, which affect glucose blood levels, into clinical practice can be a cutting-edge development in treatment of type 2 diabetes.

Innovative FGF1 protein analogues in the treatment of type 2 diabetes

Fibroblast growth factor 1 (FGF1) is an autocrine and paracrine regulator which plays an important role in the proliferation processes. Latest reports confirm its effect on glucose homoeostasis, and therefore creation of an analogue of this protein seems to be an attractive therapeutic objective. Celon Pharma is conducting research aiming at developing an innovative FGF1 analogue which could become a breakthrough therapy in type 2 diabetes.