Multiple Sclerosis Treatment: SOX10 – another hope

New opportunities in the treatment of multiple sclerosis

NanoNewsNet based on UB materials: ‘Master switch’ for myelination in human brain stem cells is identified

Scientists from the University of Buffalo (University at Buffalo, UB) have discovered a transcription factor that initiates the most important process of myelination for the brain. The study is published online in Proceedings of the National Academy of Sciences: Jing Wang et al., Transcription factor induction of human oligodendrocyte progenitor fate and differentiation.

The identification of this factor, SOX10, in human brain cells brings scientists closer to the possibility of treating multiple sclerosis by transplanting myelin-synthesizing brain cells to patients.

"Now that we have identified SOX10 as the initiator of myelination, we can begin to develop a viral or pharmaceutical approach to its administration to patients with multiple sclerosis," says study leader Fraser Sim, PhD, associate professor of Pharmacology and Toxicology at the School of Medicine and Biomedical Sciences (School of Medicine and Biomedical Sciences) UB. "If we manage to create a drug based on a low molecular weight compound that will activate SOX10, it will have great therapeutic value."

The treatment of multiple sclerosis with stem cell-based methods is considered a very promising direction, but the successful development of this approach is hindered by several serious obstacles, first of all, the too long duration of time required for progenitor cells to differentiate into myelin-synthesizing oligodendrocytes. So, if we use the currently available methods, obtaining the number of human oligodendrocytes sufficient to treat one patient can take a whole year.

This is partly due to the multi-step nature of the process: first, skin or blood cells must be reprogrammed into induced pluripotent stem cells capable of differentiating into any type of cell, from which neural progenitor cells are obtained. Then the neural progenitor cells must undergo differentiation into oligodendrocyte progenitor cells that can finally become oligodendrocytes.

"Ideally, we would like to have oligodendrocyte progenitor cells right away," explains Dr. Sim. "The new data we have obtained is a stepping stone to the ultimate goal - to take skin or blood cells of the patient and create oligodendrocyte progenitors from them."

Using fetal (non-embryonic) brain stem cells, UB scientists "discovered the hunt" for transcription factors that are absent in neural progenitor cells and active in oligodendrocyte progenitors.

Although neural progenitor cells are capable of synthesizing myelin, they do it very poorly and can cause undesirable effects for patients, so the only candidate for transplantation are oligodendrocyte progenitors.

"An oligodendrocyte progenitor cell is an ideal cell for transplantation," says Dr. Sim. "The question was whether we could use one of these transcription factors to transform neural progenitor cells into oligodendrocyte progenitors."

To get an answer to this question, the researchers studied various characteristics, such as the expression of mRNA, the expression of proteins and all genes, and the results of functional studies. Eventually, the list of transcription factors expressed exclusively by oligodendrocyte progenitor cells narrowed to 10.

"Of all the 10 factors we studied, only SOX10 was able to make the transition from a neural progenitor to an oligodendrocyte progenitor," Dr. Sim comments.

In addition, the researchers found that SOX10 can accelerate the differentiation of an oligodendrocyte progenitor cell into an oligodendrocyte.

According to Dr. Sim, this is a remarkable result, since one of the biggest problems with multiple sclerosis is that the cells "get stuck" at this stage.

"With multiple sclerosis, the immune system primarily attacks the brain, which cannot recover effectively," explains the scientist. "If, by promoting the formation of oligodendrocytes from progenitor cells, we were able to enhance regeneration, we would be able to keep patients at the recurrent-remitting, much less severe than the later progressive stage of the disease."

Portal "Eternal youth" http://vechnayamolodost.ru 09.07.2014