Diseases of the central nervous system (CNS)

One of the greatest challenges is to understand the functions of the human brain and several fundamental mechanisms remain elusive. Understanding the neuronal networks of the brain will be of utmost importance to generate effective drugs for diseases of the central nervous system such as epilepsy, mood disorders and neurodegenerative disorders such as Alzheimer’s and Huntington’s diseases.

For CNS diseases, lack of efficacy is a major cause for failures in late stage clinical trials, leading to unmanageable costs for drug development. Therefore there is an urgent demand for better, more clinically-relevant methods for selecting compounds for clinical trials. Although modern neurobiology, encompassing molecular, genetic and single cell recording techniques, has been valuable, using primary cells and native tissue based models that recapitulate the full physiological properties of neurons and neuronal networks is likely to be a more powerful method. With our partners, our approach is to utilize techniques for registering communication between neurons in an efficient way to identify novel candidate compounds for treating diseases of the CNS and neurodegenerative disorders in general.

To generate clinically-relevant data for our partners, we employ phenotypic screening using primary neuronal cell cultures and the state-of-the-art Cellaxess Elektra electric field stimulation discovery platform. The neurons readily form neuronal networks in vitro and by using optical probes to register changes in membrane potential (for example), we can detect changes in the phenotype of interest. With this approach we can identify compounds affecting both known and unknown targets involved in neuronal excitability as well as synaptic function and other changes at the network level.

An important aspect of our service capabilities, is the ability of designing assays with cells of human origin, including cells derived from inducible pluripotent stem cells (iPSC). We are using our platform as a valuable tool for functional phenotypic screening campaigns using disease-specific neurons derived from primary cells, tissues and patient iPSCs. This allows for screens of substances that can directly alter the function of affected neurons in specific CNS diseases.