The day in which doctors can grow 'mini brains' from your skin cells to test which drug suits you best is edging closer.
A team of researchers from the University of Cambridge has developed ‘mini-brains’ that allow them to examine a deadly and untreatable neurological condition called amyotrophic lateral sclerosis (ALS) that causes paralysis and frontotemporal dementia (FTD) and affects younger people primarily after the age of 40-45. And for the first time, they were able to grow the mini-brains for nearly a year, effectively tracking the evolution of the disease forming and spreading.
This could help researchers understand what happens in the earliest stages of the disease, long before symptoms appear, and help them test for new drugs and treatments.
Mini-brains grew for 240 days
Scientists employed stem cells taken from people suffering from ALS/FTD to grow the mini-brains for 240 days — and what's more, the team has grown them for 340 days in an unpublished work. This is a significant step forward since previous studies were able to grow them for only a relatively short time frame, according to the study published today in Nature Neuroscience.
This procedure often involves removing cells from a patient’s skin and reprogramming them back to their stem cell stage, which is basically their infant stage where they have the capacity to turn into most types of cell. These can then be produced in culture as 3D clusters that imitate certain organ elements, allowing researchers to see how cellular alterations lead to disease.
"Neurodegenerative diseases are very complex disorders that can affect many different cell types and how these cells interact at different times as the diseases progress," said Dr. András Lakatos, the senior author who led the research, in a press release. "To come close to capturing this complexity, we need models that are more long-lived and replicate the composition of those human brain cell populations in which disturbances typically occur, and this is what our approach offers. Not only can we see what may happen early on in the disease – long before a patient might experience any symptoms – but we can also begin to see how the disturbances change over time in each cell."
What was the trick?
The organoids are usually grown as balls of cells. In the new study, however, the researchers generated slice cultures, and this technique assured that most cells in the model received the nutrients they needed to stay alive. The researchers were able to detect alterations in the organoids' cells at an early stage, such as cell stress, DNA damage, and changes in how DNA is transcribed into proteins. The astroglia, a type of nerve cell that orchestrates muscle movements and mental functions, were damaged by these modifications.
"Although these initial disturbances were subtle, we were surprised at just how early changes occurred in our human model of ALS/FTD," added Dr. Lakatos. "This and other recent studies suggest that the damage may begin to accrue as soon as we are born. We will need more research to understand if this is, in fact, the case, or whether this process is brought forward in organoids by the artificial conditions in the dish."
While there are currently no effective treatments for ALS/FTD, this discovery provides a glimmer of hope that, in the future, it may be possible to prevent or delay the disease's progression. Scientists may be able to uncover more possible drug targets by modeling some of the mechanisms that contribute to DNA damage in nerve cells and illustrating how these can lead to various cell dysfunctions.