Nav: Home

First clues to the causes of multiple sclerosis

May 15, 2018

Multiple sclerosis, which affects 1 in 1,000 people, is frequently characterised by relapses associated with variable functional impairments including among others vision problems, impairment of locomotor functions or difficulties with speech. There is still no cure for multiple sclerosis, with current treatments largely based on managing symptoms, especially accelerating recovery phases following a relapse and reducing the number and severity of relapses. Researchers at the University of Geneva (UNIGE), Switzerland, and Geneva University Hospitals (HUG) have identified a DNA-binding factor called TOX that might play a role in triggering multiple sclerosis. They found that TOX license immune cells to cause autoimmune tissue destruction in the brain. The results of the research, published in the journal Immunity, deliver important insights into our understanding and treatment of auto-immune diseases.

Multiple sclerosis is as much of a mystery today as it has always been. We know that genetic risk factors but also environmental ones such as infection or even smoking are known to play a role in the development of the disease. However, it is still not known why it is triggered in some cases and not in others. "We decided to analyse the infectious factors by studying the auto-immune reactions provoked by different pathogens," explains Doron Merkler, Professor in the Pathology and Immunology Department in UNIGE's Faculty of Medicine and in the HUG Clinical Pathology Department. "This was to try to pinpoint an element that might influence the development of multiple sclerosis where there has been an infection".

Viral pathogen versus bacterial pathogen

The UNIGE researchers selected two distinct pathogens that elicit a response from the immune system - one viral and one bacterial - which were then injected into healthy mice. "We saw a quantitatively identical immune reaction from the lymphocytes called CD8+ T," says Nicolas Page, a researcher in UNIGE's Pathology and Immunology Department. "However, only the mouse infected with the viral pathogen developed an inflammatory brain disease reminiscent to Multiple Sclerosis."

Based on these outcomes, the scientists analysed how the expression of the genes in the CD8+ T cells varied according to the pathogen used to activate them. This helped them identify TOX, a DNA-binding factor expressed only in the cells activated by the viral pathogen. "We found that the inflammation environment influences the expression of TOX in T lymphocytes, and that it could play a role in triggering the illness," continues Page.

Nothing stops TOX

The immunologists validated the link between TOX and multiple sclerosis in the experimental model by eliminating the expression of this DNA-binding factor in the CD8+ T lymphocytes of healthy mice. "And, although they received the viral pathogen, the mice did not develop the disease," mentioned Merkler.

What, then, is the role of TOX in setting off multiple sclerosis? "Our brains have a limited regenerative capacity," says Merkler, "which is why they have to protect themselves against the body's immune reactions, which can destroy its cells by wanting to fight the virus, creating irreversible damage. The brain then sets up barriers that block the passage of T lymphocytes." However, by altering the expression of some of the receptors on the surface of the CD8+ T lymphocytes responsible for receiving the blocking signals sent by the brain, TOX enables the cells to cross the safeguards and attack the brain cells, causing the outbreak of the disease.

A step towards a better understanding of multiple sclerosis

Following these analyses, the UNIGE researchers noted that TOX was also expressed in T cells present in multiple sclerosis lesions. "This is an encouraging result for understanding the causes of the disease but there is still lots of work to be done to ascertain what really causes multiple sclerosis in humans," admits Page. The UNIGE researchers will now target the functioning of TOX and its involvement in other auto-immune diseases as well as in some types of cancer.
-end-


Université de Genève

Related Multiple Sclerosis Articles:

New biomarkers of multiple sclerosis pathogenesis
Multiple sclerosis (MS) is a chronic debilitating inflammatory disease targeting the brain.
Using telemedicine to treat multiple sclerosis
Multiple sclerosis (MS) clinicians face continued challenges in optimizing neurological care, especially for people with advanced MS living in medically underserved communities.
Improving symptom tracking in multiple sclerosis
With a recent two-year, $833,000 grant from the US Department of Defense, kinesiology professor Richard van Emmerik and colleagues at the University of Massachusetts Amherst hope to eventually help an estimated 1 million people worldwide living with progressive multiple sclerosis by creating an improved diagnostic test for this form of the disease, which is characterized by a steady decrease in nervous system function.
An antibody-based drug for multiple sclerosis
Inserm Unit U919, directed by Professor Denis Vivien has developed an antibody with potential therapeutic effects against multiple sclerosis.
Four new risk genes associated with multiple sclerosis discovered
Scientists of the Technical University of Munich and the Max Planck Institute of Psychiatry have identified four new risk genes that are altered in German patients with multiple sclerosis.
PET detects neuroinflammation in multiple sclerosis
The triggers of autoimmune inflammation in multiple sclerosis (MS) have eluded scientists for many years, but molecular imaging is bringing researchers closer to identifying them, while providing a means of evaluating next-generation therapies for MS, say researchers introducing a study at the 2016 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging.
Scientists find genetic cause of multiple sclerosis
Researchers have discovered a rare genetic mutation that makes it probable that a person will develop multiple sclerosis (MS).
ANKRD55: A new gene involved in Multiple Sclerosis is discovered
The Ikerbasque researcher Koen Vandenbroeck, who heads the Neurogenomiks laboratory which reports to the Achucarro centre and the UPV/EHU-University of the Basque Country, together with other national and international groups, has shown that a genetic variant in the 5q11 chromosome, which is associated with susceptibility to developing multiple sclerosis, greatly regulates a gene known as ANKRD55.
Children with and without multiple sclerosis have differences in gut bacteria
In a recent study, children with multiple sclerosis had differences in the abundance of specific gut bacteria than children without the disease.
Rituximab is superior to fingolimod for certain patients with multiple sclerosis
A new study indicates that rituximab is more effective than fingolimod for preventing relapses in patients with highly active multiple sclerosis switching from treatment with natalizumab.

Related Multiple Sclerosis Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...