Brain steroid clue to multiple sclerosis

According to the Daily Mirror there is a “daily pill to prevent or even cure multiple sclerosis in the pipeline”. The newspaper says that “experts are ready to start human trials on the pills and hope they could be widely available within seven years”.

In multiple sclerosis (MS) patients experience damage to the protective coating around nerve cells, called myelin sheaths. These sheaths protect the part of the cell, called the axon, responsible for sending signals to other nerve cells. Damage to the myelin sheath, and subsequently to the axon, prevents the brain and spinal cord from communicating with each other.

Although the underlying cause of MS is not known, in recent years researchers have begun considering the role that certain naturally occurring brain steroids may play in the condition. In this latest animal study researchers examined how mice with a multiple-sclerosis-like disease responded to daily injections of a steroid called allopregnanolone, which is normally found in the brain.

The results of this study appear to be promising but, as it is a preliminary study, further research in humans is needed before we will know if the results apply to human disease. Also, even if brain steroids are eventually found to have some therapeutic role in MS treatment, it is unclear how this injected substance could be developed into a pill.

Where did the story come from?

The study was carried out by researchers from the University of Alberta in Canada, Stanford University in the US and Tehran University of Medical Sciences in Iran. The research was funded by the Canadian Institutes for Health Research, the Alberta Heritage Foundation for Medical Research and the Multiple Sclerosis Society of Canada.

The study was published in the peer-reviewed medical journal Brain.

Most media sources reported the research fairly accurately, with the Daily Mirror reporting that the research was carried out in mice and that human studies have not yet started.

What kind of research was this?

This was a controlled animal experiment using a mouse model of multiple sclerosis to examine the potential actions of effects of a steroid on disease progression.

Within our DNA there are sections called genes that contain the instructions for making specific substances. However, these genes are not always ‘expressed’. This means that our bodies do not always produce the substances our genes contain the instructions for. The researchers examined the role of a specific molecule called micro-RNA (miRNA), which is responsible for controlling the expression of genes, and which also plays a role in the development of diseases of the nervous system. The researchers say that previous research has shown that miRNAs are involved in the development of MS. They sought to identify which biological substances had their production regulated by these miRNAs, and to examine how replacing underproduced substances affected disease severity, nerve cell damage and inflammation in an MS model.

Animal experiments of this kind are useful for preliminary studies that would not be feasible to conduct in humans. However, further studies are needed to confirm that any results will hold true in humans.

What did the research involve?

The researchers examined the brains of MS patients and other people without MS, quantifying the amount and types of miRNAs present in their brains. They found miRNAs that suppress the expression of protective brain steroids called ‘neurosteroids’, and that the action of miRNAs led to significantly lower levels of these neurosteroids in the brains of MS patients compared with non-MS patients. They determined that the production of a neurosteroid called allopregnanolone was most affected by these miRNAs, and set it as a target for the next phase of their study.

A mouse MS model was then used to examine the impact of treating mice with doses of the steroid allopregnanolone, specifically looking at how this affected inflammation of nervous system tissue and MS disease severity. The mice were injected with either a steroid or a control molecule every day for up to 30 days. The researchers measured the amount of various steroids present in the mice’s brains, as well as the functioning of the pathways that normally produce the steroid. In addition, they measured the severity of the disease and the damage done to key nerve structures called the myelin sheath and the axon, which are normally injured as MS progresses in humans.

What were the basic results?

When examining brain tissue from MS and non-MS patients, the researchers found significant differences in the expression of miRNAs between the two groups. Most of these miRNAs were involved in regulating genes involved in immune responses and inflammation. Those miRNAs that target the genes involved in the creation of steroids were more present in the MS brain samples, which the researchers say indicates lower levels of production of protective or restorative steroids in these patients’ brains.

When examining the impact of treatment with the steroid allopregnanolone on disease severity and the inflammation of brain tissue, the researchers found that mice that received the steroid maintained a better protective myelin coating on the spinal cord than the mice that received the placebo. The mice treated with the steroids also showed less injury to the parts of the spinal cord cells responsible for sending signals.

Mice treated with allopregnanolone also demonstrated significantly reduced disease severity compared with both their own symptoms before treatment and with the mice that received the placebo injection.

How did the researchers interpret the results?

Based on the analysis of miRNAs in MS and non-MS brain tissue samples, the researchers say that the production of steroids in the brain, which was reduced in the MS tissue, may be important to maintaining tissue health. This steroid production seems to be disrupted by the development of MS. The researchers say that previous studies have shown that steroids created in the brain are involved in normal brain cell activity as well as diseases.

Based on the animal experiments, the researchers say that treatment with allopregnanolone reduced inflammation and prevented injury to two vital components of nerve cells, the protective coat that surrounds the fibre, and the axon. These key areas are responsible for sending signals to other nerve cells.

Conclusion

This was a complex animal experiment that examined the possible role of a specific molecule in the progression of multiple sclerosis. The researchers say that it is still unclear whether the increased expression of the miRNAs in MS patients is involved in the development of the disease or is a response to it.

The researchers say that they have identified a novel mechanism involved in the progression of MS, and that this mechanism is well suited to therapeutic interventions. However, the results of this study are based on a mouse model of MS. This is not the same as MS in humans. The model can only be an approximation of human disease. Further research is needed to confirm that the findings hold true in humans.

MS is an extremely complicated disease, and researchers and doctors do not yet fully understand its underlying causes. Previous research has shown that complex changes occur in many different biological processes, contributing to the damage done by the disease. This complexity has meant that, to date, most treatments for people living with MS are aimed at reducing relapse or episodes of increased disease activity that affect the ability to function normally.

Given the challenges presented by researching and understanding the condition in humans, it is unclear at this point whether the “simple pill” mentioned by some news sources would be sufficient “to prevent or even cure MS”.