Scientists from the University of British Columbia discovered an association between an aggressive form of multiple sclerosis (MS) and a particular genetic mutation. A team led by Dr. Zhe Wang carried out an investigation on several blood samples to try and find a genetic risk factor. The results were published in the Cell’s Neuron on June 1, 2016.

Multiple sclerosis is a chronic inflammatory, neurodegenerative disease that affects the central nervous system. It attacks and eventually destroys the myelin sheaths. The latter is a white substance that covers the center of some nerve cells. They are tasked with creating an electrical layer that provides insulin which makes them very important. In fact, they make sure everything works fine in the central nervous system (CNS).

When MS damages the myelin cover of nerve cells, the network created by the CNS is disrupted which can be seen as physical, mental and sometimes, psychiatric problems. Among the symptoms of the disease, scientists have found blindness, muscle weakness, impaired coordination and others.

Scientists from the University of British Columbia discovered an association between an aggressive form of multiple sclerosis and a particular genetic mutation. Photo credit: SBS
Scientists from the University of British Columbia discovered an association between an aggressive form of multiple sclerosis and a particular genetic mutation. Photo credit: SBS

Experts have identified two types of MS: the relapsing form and the progressive form. The first one is the less problematic of the two. A patient suffering from it will present 1 or 2 symptoms and then will get better. However, people presenting the second form are not that lucky. In these cases, symptoms pile up one after the other making life very unpleasant. In fact, according to some statistics, people diagnosed with the progressive form of MS have a shorter life expectancy. They live 5-10 years less than healthy individuals.

Diagnostic: Genetic mutation

Most scientists blame an external biological virus as the sole culprit, but others like Dr. Dessa Sadovnick think that a genetic mutation can be behind the problem. Not only the source is unknown but also doctors do not have a bullet-proof method to diagnose the disease, they will carefully study a person’s symptoms before diagnosing MS.

Since the disease attacks the central nervous system, the patient’s signs will vary depending on what part of the system is damaged; changes in sensations, like tingling or numbness, are common. Muscle weakness, muscle spasms, and difficulty in moving are usually present. Coordination skills suffer dearly and it presents in the form of problems with speech, visual difficulties or even chronic pain.

But there is another problem, in 85 percent of the cases, it begins as a clinically isolated syndrome (CIS) which means that in the first stages of the problem, doctors cannot be totally sure they are dealing with MS which reduces the effectiveness of the treatment.

There is no cure for MS yet, and the only solution provided so far is therapy. For the remission form sufferers, therapy works perfectly fine as they usually get better without complications, but for people with the progressive form things get bad real quick without much modern science can do.

“The identification of genes and mutations responsible for Mendelian forms of disease provides mechanistic insight into disease ontology and spurs the generation of physiologically relevant cellular and animal models, and the development of novel therapeutics to better treat and halt disease progression,” the paper reads.

The causes are unknown

Nobody really knows what triggers the disease, but scientists have tried to crack the puzzle and in the process, they have found some tendencies like geography. According to specialists, MS is more common in people that live far away from the equator. However, there are some exceptions such as the Sardinians and the Sicilians who are susceptible to it and live close the equator. In their search for a culprit, experts have also accused many microbes, but there is no compelling evidence that leads to thinking they trigger the disease.

Scientists still know nothing about the cause of the most common form of MS, but thanks to Dr. Wang and his team, they now know that there is a genetic mutation that makes some individuals very susceptible to the progressive form of the disease. They found a particular genetic variation which was present in people that were diagnosed with MS and rapidly developed the progressive form. However, Dr. Wang said that they were more susceptible, but the mutation (NR1H3) is not accountable for the activation of the disease.

“The clinical phenotype observed in these patients is consistent with an unusual form of MS with a relapsing-remitting onset that rapidly becomes progressive or PPMS. Although the mutation was not observed in our healthy controls, it has been described in 21 individuals from the ExAC database,” the report reads “Therefore, these families appear to have a highly susceptible NR1H3 genetic background for MS, but an initial damage may be necessary to trigger the onset of disease.”

The study was funded by many governmental institutions, such as the Canada Research Chair and the Canadian Institute of Health Research, among others. The DNA sample collection was funded by the MS Society of Canada Scientific Research Foundation.

Source: Cell