Design and development of AMPA receptor modulators with a much improved safety profile as novel drugs for treating the cognitive dysfunction associated with schizophrenia and other CNS disorders

Around 1% of the population will suffer from schizophrenia at some point in their life. Symptoms such as paranoia and/or hearing voices can be reasonably well treated by existing medications. However, these drugs have little effect on the other symptoms (lack of motivation and impaired social function) and impaired cognition, including difficulties with attention, memory and problem-solving that result in a “brain fog”. These largely untreated symptoms remain a huge barrier to the resumption of a fully functional, “normal” life for these individuals and are associated with an annual estimated cost in the UK alone of around £12 billion. Professor Simon Ward from the University of Sussex has received a Seeding Drug Discovery Award to identify and develop drug which is a selective modulator of the AMPA receptor which has the potential to provide an innovative new treatment for patients with schizophrenia. If successful the team expect to have a compound ready for clinical evaluation in just over three years time. Nerve cells (neurons) communicate with each other by releasing chemicals known as neurotransmitters that interact with proteins called receptors on adjacent neurons. Levels of the neurotransmitter glutamate, which is crucial for normal cognitive function, are altered in schizophrenia. A specific subtype of glutamate receptor, the AMPA receptor, is thought to be associated with cognition and therefore increasing AMPA receptor function should improve cognitive performance in schizophrenia and thereby addressing an unmet need and revolutionizing the functional outcome of this patient population.