It is known that MS is caused by a mixture of genetic and environmental risk factors. Now investigators in the US have developed an approach to systematically test the effects of hundreds of environmental factors on inflammation in the brain.
MS is a complex disease which arises 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. However, studies in identical twins have shown that genetics alone is not enough (as, if one identical twin has MS, the other twin only has a one in four chance of developing MS) and 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 sheer number of different chemicals and other factors we are exposed to each day of our lives.
But by understanding the risk factors for MS we might hopefully be able to prevent it as well as develop better ways to treat it.
As part of funding from 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 whether they may play a role. They have recently published their findings in the prestigious scientific journal Cell.
They 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 water of the fish and evaluating the effects on inflammatory genes in the fish. They found that five of the compounds increased the activity of nos2a, a zebrafish gene associated with inflammation.
Once they had narrowed the list to five compounds, they tested these on mice cells grown in a laboratory. In particular they tested these compounds on the immune cells of the brain to see whether they would increase the activity of the equivalent gene in mice, Nos2. They found that two out of the five chemicals, a herbicide known as linuron and a chemical used by various industries called methyl carbamate, led to an increase in Nos2. Linuron has recently been banned in Europe because of its risk to mammals. Both chemicals boosted Nos2 and 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.
The researchers traced which genes in the mouse brain cells were responding to linuron and, using a mouse model of MS (known as experimental autoimmune encephalomyelitis), showed that blocking the genes that were responding to linuron prevented the activation of the immune 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 activity of genes that respond 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 and see whether it does in fact contribute to MS.
This study developed a novel way to screen hundreds of environmental chemicals at once and created a pathway for testing to determine whether they might be involved in MS, providing an important tool for the International Progressive MS Alliance going forward. The International Progressive MS Alliance is a collaboration between MS organisations, researchers, clinicians, pharmaceutical companies, and people with progressive MS that aims at transforming the landscape for people with progressive forms of MS.