A common form of motor neurone disease, amyotrophic lateral sclerosis, often overlaps with frontotemporal dementia (ALS/FTD) and can affect younger people, occurring mostly after the age of 40-45. These conditions cause devastating symptoms of muscle weakness with changes in memory, behaviour and personality. Being able to grow small organ-like models (organoids) of the brain allows the researchers to understand what happens at the earliest stages of ALS/FTD, long before symptoms begin to emerge, and to screen for potential drugs.
In general, organoids, often referred to as ‘mini organs’, are being used increasingly to model human biology and disease. At the University of Cambridge alone, researchers use them to repair damaged livers, study SARS-CoV-2 infection of the lungs and model the early stages of pregnancy, among many other areas of research.
Typically, researchers take cells from a patient’s skin and reprogramme the cells back to their stem cell stage – a very early stage of development at which they have the potential to develop into most types of cell. These can then be grown in culture as 3D clusters that mimic particular elements of an organ. As many diseases are caused in part by defects in our DNA, this technique allows researchers to see how cellular changes – often associated with these genetic mutations – lead to disease.
Scientists at the John van Geest Centre for Brain Repair, University of Cambridge, used stem cells derived from patients suffering from ALS/FTD to grow brain organoids that are roughly the size of a pea. These resemble parts of the human cerebral cortex in terms of their embryonic and fetal developmental milestones, 3D architecture, cell-type diversity and cell-cell interactions.
Image: Mini brain organoids showing cortical-like structures
Credit: Andras Lakatos
Reproduced courtesy of the University of Cambridge