A step forward in finding a treatment for a deadly neurological disorder


MRI section of a brain affected by ALS with the front section of the brain highlighted

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a nasty disease that steadily attacks nerve cells in the brain and spinal cord. It’s pretty much always fatal within a few years. As if that wasn’t bad enough, ALS also can overlap with a condition called frontotemporal dementia (ALS/FTD). Together these conditions cause devastating symptoms of muscle weakness along with changes in memory, behavior and personality.

Now researchers at Cambridge University in the UK have managed to grow groups of cells called “mini-brains” that mimic ALS/FTD and could lead to new approaches to treating this deadly combination.

We have written about these mini-brains before. Basically, they are created, using the iPSC method, that takes skin or blood cells from a patient with a particular condition, in this case ALS/FTD, and turns them into the kind of nerve cells in the brain affected by the disease. Because they came from someone who had ALS/FTD they display many of the characteristics of the disease and this gives researchers a great tool to study the condition.

This kind of approach has been done before and given researchers a glimpse into what is happening in the brains of people with ALS/FTD. But in the past those cells were in a kind of clump, and it wasn’t possible to get enough nutrients to the cells in the middle of the clump for the mini-brain to survive for long.

What is different about the Cambridge team is that they were able to create these mini-brains using thin, slices of cells. That meant all the cells could get enough nutrients to survive a long time, giving the team a better model to understand what is happening in ALS/FTD.

In a news release, Dr András Lakatos, the senior author of the study, said: “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.

“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.”

Thanks to these longer-lived cells the team were able to see changes in the mini-brains at a very early stage, including damage to DNA and cell stress, changes that affected other cells which play a role in muscle movements and behavior.

Because the cells developed using the iPSC method are from a patient with ALS/FTD, the researchers were able to use them to screen many different medications to see if any had potential as a therapy. They identified one, GSK2606414, that seemed to help in reducing the build-up of toxic proteins, reduced cell stress and the loss of nerve cells.

The team acknowledge that these results are promising but also preliminary and will require much more research to verify them.

CIRM has funded three clinical trials targeting ALS. You can read about that work here.

One thought on “A step forward in finding a treatment for a deadly neurological disorder

  1. The process of cell development and progressive acquisition of specialized functioning phenotype require intracellular communication. Investigate showed that several parameters can influence development processes of cell, such as physical parameters, extracellular matrix components, cell adhesion molecules and membrane junction complexes between apposing cells. It was later proved that growth factors played key roles for cell development and functioning. Cells require growth factors to bind to cellular receptors and initial intracellular stimulus for signal tranduction network. These events are important to activate many potential protooncogenes to regulate cell proliferation, differentiation and behavior. As all specific cell types process a variety of growth factor receptors suggests that cell development and behavior in vivo are determined by combinations of interacting stimuli. For instance, recruitment of cultured fibroblasts BALBc/3T3 into cell cycle. The G0 phase cells require mitogenic response of PDGF to advance into G1 phase. Subsequently, combination of EGF and IGF are essential to commit for DNA synthesis. Neither EGF nor IGF alone constitutes a mitogenic signal but the mixture of two factors stimulate complementary components of the signal transduction network to control developmental processes. In addition, growth factor PDGF has ability to mediate transmodulation of EGF receptors inSwiss/3T3 cells. The up-or down-regulation of growth factor receptors may result in transition of a rapid switch from insensitivity to high sensitivity by controlling the amplifying of growth factor response. In primary cultures of oligodendrocyte type 2 astrocyte, they require PDGF and FGF to induce proliferation and decision of differentiation is altered by the availability of stimuli to produce TGF-β and inhibit cell proliferation.

    Cells require growth factors for survive, proliferation, differentiation and functioning. Cells require both homologous and heterogeneous cells to produce growth factors for growth and functioning. The arrangement of different developing cell types in tissues and organs showed cell-cell communication are important for cell development. The inability of three-dimension structure of organoids for vascularization process may cause inner part of cells to develop hypoxia and form unhealthy cells. However, growing a thin layer of cells without couple with heterogeneous neighboring cells may neglect some essential growth factors for cell requirement. Therefore, results of unhealthy cells may hinder the developing of effective therapeutic treatment for cell-based therapy .

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