A usually supportive brain cell is responsible for cell death in motor neuron disease patients, according to a new study.
An international team of scientists, led by the University of Sheffield, England, has discovered that the oligodendrocyte brain cell has a crucial role in the progression of the degenerative disease.
The study, published in the latest edition of Proceedings of the National Academy of Sciences, also showed that reducing levels of SOD-1, a gene that has been linked to causing MND, can rescue the adverse effect on motor neurons.
The researchers, led by Dr Laura Ferraiuolo from the Sheffield Institute of Translational Neuroscience (SITraN), who began the research at The Kaspar Laboratory based at the Centre for Gene Therapy at the Research Institute at Nationwide Children’s Hospital (RINCH) in Columbus, Ohio, developed a novel oligodendrocyte in vitro model from the skin cells of MND patients.
It is the first human in vitro model that enables scientists to study the specific interaction between neurons and oligodendrocytes from MND patients.
“The ability to model the communication between the cells dying during the disease, the motor neurons, and their surrounding neighbouring cells is crucial for the development and timing of the therapies,” she said.
“With this rapid reprogramming protocol, we are a step closer to personalised medicine.”
Previous studies have concluded that other human cells supporting motor neurons, such as astrocytes and microglia, are likely to contribute to motor neuron death in MND. This breakthrough comes from observations in both mouse and human oligodendrocytes following the development of “the direct conversation” method, developed by Professor Brian Kaspar and his team at the Kaspar Laboratory.
This technique allows skin cells from living MND patients to be programmed into neural progenitor cells, which have the potential to be differentiated into different types of cells such as astrocytes, oligodendrocytes and neurones.
In this latest study, neural progenitor cells were differentiated into oligodendrocytes, which were derived from skin cells collected from both patients with familial MND, those with a family history of the disease, and sporadic MND.
The results showed that oligodendrocytes from both familial and sporadic MND patients result in motor neuron death.
Oligodendrocytes from healthy individuals or from those suffering from other neuromuscular disorders did not harm motor neurons.
Senior author Professor Kaspar said: “By using this novel direct conversational method, in the past few years we have been able to interrogate the function of different glial cells in MND and we have started understanding that different supporting cells ‘go-rogue’ at different stages of the disease and contribute to the pathology through different mechanisms.”
Ferraiuolo L, Meyer K, Sherwood T et al. Oligodendrocytes contribute to motor neuron death in ALS via SOD1 dependant mechanism. PNAS. September 2016.
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