Using neurons grown from stem cells, EU-funded researchers are revealing more about mutations that lead to autism, schizophrenia and intellectual disability which researchers hope will lead to new drug targets for personalised medicine.
© J.H.P Broeke, 2016
Autism, schizophrenia and intellectual disability affect more than 1 % of the population. These conditions greatly affect quality of life and result in direct and indirect costs of EUR 150 billion per year in Europe alone.
The latest genetic findings have revealed that mutations affecting the function of synapses – the junctions between neurons in the brain – can lead to autism, schizophrenia and intellectual disability occurring together. Consequently, overlapping symptoms make accurate diagnosis difficult, leaving intervention patchy and ineffective.
Scientists working on the EU-funded COSYN project are now looking to capitalise on the latest research to search for a way to diagnose and treat patients with these comorbid disorders. Their work in the fields of genomics, neurobiology and stem cell biology could pave the way for effective precision medicines for these patients.
‘We’re not looking for a therapy that will fix everybody with the condition,’ says project coordinator Patrick Sullivan of the Karolinska Institute in Sweden. ‘We want to make one therapy for one person – a person with a combination of these illnesses and with a causal mutation in a gene that functions in the synapse.’
Difficult to extract
In their search for potential treatments, the COSYN team is studying the genetic and molecular pathways inside neurons that lead to the development of these disorders.
But what makes studying people with brain conditions such as autism, schizophrenia and intellectual disability difficult is that it is almost impossible to acquire living tissue for examination: neurons are extremely hard to extract from a living brain which means that the only alternative is to extract them after a patient's death.
To date, the core activity of the COSYN project has been identifying patients with two or more of the conditions, then harvesting cells from easy-to-access areas such as their skin or blood. These cells have then been reprogrammed into human induced pluripotent cells. These patient-derived stem-like cells – known for their ability to differentiate into virtually any human cell type – were then cultured in conditions that allowed them to differentiate into neurons. These neurons represent cell models that can now be used to study what is happening at the synapse. Using genome-editing technologies, the COSYN team will attempt to create or correct disease-causing mutations to find useful targets for medicines.
Blazing new ground
In the latter stages of the project, the COSYN team will be scaling up the cell models to make them available for industry-standard compound screening. Working closely with pharmaceutical partners, researchers will be creating case studies in precision medicine, using neurons derived from a specific patient to evaluate the effectiveness of a given medication.
‘We’re trying to blaze new ground here,’ says Sullivan. ‘We’re creating a model to encourage more investment from industry – the people who know how to bring to the market safe and effective medicinal products – and also to encourage start-ups and people looking to do more risky versions of this to give it a go, too.’
