Screening environmental chemicals that may influence MS

• MS is thought to develop through a complex interaction of genetic and environmental factors.

• Scientists have developed a novel way to screen hundreds of environmental chemicals at once.

• After screening 976 chemicals, they identified two that may potentially contribute to MS.

MS is a complex disease which occurs when the immune system mistakenly attacks the protective myelin sheath coating on nerve fibres. Exactly what triggers this autoimmune process in each individual is unclear. Studies in identical twins have shown that genetics alone is not enough to explain this. If one identical twin has MS, the other twin only has a one in four chance of developing MS, meaning that environmental factors must play an important role.

However most epidemiological studies have failed to show any strong links between environmental chemicals and the development of MS, with the exception of smoking.  Identifying these environmental chemical risk factors is challenging given the high number of different chemicals and other factors that we are exposed to everyday. By understanding the risk factors for MS, we may be able to prevent it as well as develop better ways to treat it.

As part of a study funded by the International Progressive MS Alliance, a group of scientists based at the Brigham and Women’s Hospital in Boston, USA have developed an innovative way to screen hundreds of chemicals to see if they play a role. They have recently published their findings in the scientific journal Cell.

Testing in zebrafish and mice cells

The researchers started with a list of 976 chemicals provided by the United States’ Environmental Protection Agency (EPA), which included a broad collection of representative chemicals ranging from industrial and consumer products to food additives.

Using bioinformatics, they identified a subset of 76 of these chemicals that might affect immune signals in the body. They then tested each of these 76 chemicals on zebrafish, by adding each chemical to the fish’s water and evaluating the effects on their inflammatory genes. They found that five of the compounds increased the activity of nos2a, which is a zebrafish gene associated with inflammation.

Once they had narrowed the list to five compounds, the researchers tested these on mice cells grown in a laboratory. In particular they tested the compounds on the immune cells of the brain to see if they would increase the activity of the equivalent gene in mice, which is called Nos2. They found that two of the chemicals, an herbicide known as linuron, and a chemical used by various industries called methyl carbamate, increased the activity of the Nos2 gene.   Linuron is a herbicide used in crop cultivation to suppress grass and weeds.  Methyl carbamate is a chemical used by many industries in polymers, pharmaceuticals and insecticides; in particular it is used in the textile industry to make fabric more durable.

Both chemicals also boosted two other important signals in the immune system, IL-1b and TNF-a, suggesting that these chemicals might create an environment in the brain that promotes disease. Linuron has recently been banned in Europe because of its risk to mammals.

The researchers traced which genes in mouse brain cells responded to linuron. By using experimental autoimmune encephalomyelitis, which is an engineered mouse model that looks to simulate the biology of MS,  they found that blocking the genes that were responding to linuron prevented the activation of the cells. Finally, to ensure this was relevant to people with MS, the scientists looked at brain samples of people with and without MS and found higher levels of gene activity in response to linuron, suggesting that these genes contribute to MS, and that linuron may also contribute to MS.

The scientists point out that further studies would need to be carried out to evaluate the impact of linuron in the environment on humans, to understand if it does in fact contribute to MS.

This study developed a novel way to screen hundreds of environmental chemicals at once as well as creating a pathway for testing to determine whether they might be involved in MS. It provides an important tool for the International Progressive MS Alliance going forward. The International Progressive MS Alliance is a collaboration of MS organisations, researchers, clinicians, pharmaceutical companies and people with progressive MS, that aims to transform the landscape for people with progressive forms of MS.

With thanks to MS Research Australia – the lead provider of research summaries on our website.