Wednesday, 1 June 2011

MS research roundup June 2011

This month's research roundup includes several studies on treatments for MS, particularly Natalizumab (Tysabri). As usual, I'll do my best to arrange the post with risk factors for MS first, then symptoms, diagnosis and treatment.

It's still pretty obscure what causes MS, but researchers in the USA may have gone some way to finding out. It has long been suspected that there is a genetic component to MS, but the relationship is not simple. This study looked at the way a range of environmental factors such as metabolism and Vitamin D-3 levels interacted with four genes (interleukin-7 receptor-alpha, interleukin-2 receptor-alpha, MGAT1 and CTLA-4) to affect certain proteins that regulate the disease. They found that adding Vitamin D-3 or a simple sugar called GlcNAc could help to restore proteins to their normal functions. Sounds like a very promising line of research, and one that could potentially solve the mystery of MS causation.

Spanish researchers have looked at all previous studies investigating links between having been previously infected with Epstein-Barr virus (which causes glandular fever / mononucleosis) and MS, and confirmed that having antibodies to the virus means a higher likelihood of developing MS. The timing of the infection (how long ago) was not relevant. Further research is needed, though - ideally following a group of people from before any of them develop MS symptoms.

I've observed in the past that a high proportion of people with MS seem to be (cigarette!) smokers. A group of Swedish researchers have found that smoking interacts with two genetic factors, having a gene called human leukocyte antigen DRB1*15 and not having human leukocyte antigen A*02.Smokers with both genetic risk factors were 13.5 times as likely to develop MS as non-smokers with neither. The researchers believe that cigarette smoke acts in the lungs to "prime" the immune system and make MS more likely.

Many of us who have MS are fully aware that stressful life events can make our symptoms worse. But can stress cause MS in the first place? No, say researchers from the USA and Norway. They used data from two study of nurses' health, which started in 1976 and 1989. Participants were asked to report their level of stress at work and at home. The researchers found no link between self-reported stress and MS risk. As ever though, more research is needed.

We are used to MRI imaging being used to identify MS lesions, but Italian researchers have found that people with MS also experience atrophy (wasting away) of the brain and spinal cord. The amount of atrophy is linked to the degree of disability. They suggest that in the future MRI could be used to monitor response to treatment.

Now on to treatments, and as I said above several studies on Tysabri have reported this month. There have (quite rightly) been concerns about the risk of developing the potentially fatal brain infection progressive multifocal leukoencephalopathy (PML) while using Tysabri. PML is caused by the reactivation of a virus called Polyomavirus JC (JC virus) in the nervous system. JC virus is carried by many people, and is harmless unless the person has lowered immunity.

A number of different research groups gave conference reports on Tysabri and PML. One group has developed a blood test to check whether there has been previous infection with JC virus: it's thought that these patients will be at higher risk of PML when taking Tysabri, a risk that they must take into account when deciding whether or not to take the medication. Another study confirmed that having been on another immunosuppressant therapy at any point before Tysabri increases the risk of PML.

Although PML is unquestionably serious, survival rates among those who develop it while on Tysabri seem to be better than those with other conditions (such as AIDS), possibly due to the development of modern anteretroviral drugs. Most people with MS who develop PML will survive.

People of African descent who get MS typically have a more severe disease course than average, and are less likely to respond to treatment with interferon-beta. American researchers looked at data for Tysabri use in this group of patients, and confirmed that it worked well, reducing relapse rate by an average of 60% and lesion accumulation by 79%.

Because of the risk of PML, some doctors recommend breaks in treatment with Tysabri. A group of researchers in Canada found that disease activity (measured by relapse rate and lesion growth) returned very rapidly after Tysabri was discontinued, whether or not another treatment was started.

Two studies, in Holland and Germany, followed women who became pregnant while taking Tysabri. Both studies were small, as they included only accidental pregnancies: at the moment women on Tysabri are advised not to get pregnant. Out of a total of 37 pregnancies, 28 were completely normal, 5 ended in miscarriage and one woman had a termination: one child was born with an extra finger. These data are promising, but a much larger study is needed before it can be confirmed that Tysabri is safe in pregnancy.

The increased risk of developing PML while on Tysabri, which is highly successful at slowing disease progression, illustrates the need to balance the risks and benefits of any treatment. Australian researchers have found that MS patients are often prepared to take more risks than their doctors in terms of possible side-effects. This illustrates the importance of healthcare professionals listening to the priorities and views of their patients.

Now on to other treatments. The first treatment for MS, interferon-B, was developed and trialled in the late 1980s. A group of American researchers have tracked down participants in the original trials to see howthey had fared since then. The researchers found that those who received interferon-B were only half as likely to have died as those who received a placebo. It's not clear yet what accounts for this difference, as all the participants were likely to have been on other drugs subsequently. A very significant difference though, and one that needs to be investigated further.

There have been concerns about side-effects from the new oral treatment fingolimod (Gilenya), including a risk of lowered heart rate and a condition called AV block. An American study found that these effects were transient, and usually resolve within six hours without treatment. People should be screened for heart abnormalities before taking Gilenya, though, and carefully observed after the first dose.

Spanish researchers have found that Viagra dramatically reduces symptoms in animals with a condition similar to MS. They are hoping to begin clinical trials soon. I'll be interested to see the results. MS can cause sexual dysfunction, and many men with MS are prescribed Viagra. I've not heard of any of them having "miracle cures" from MS...

It's been found that less than half of people with MS are still consistently taking their disease-modifying drugs after 2 years, possibly because of side effects or people perceiving no benefit from them. What is needed, as we all know, is a cure. Excitingly, American and Chinese scientists have succeeded in making human stem cells convert into astrocytes, the cell type which promotes myelination. In my view, stem cell research is what will eventually provide a cure for MS, and this is a major step forward.

Finally - and, I'm afraid, rather depressingly - some British research into the use of antidepressants in MS. Although treatment with antidepressants was always preferable to no treatment, there was no definite evidence that quality of life was improved as a result. Depression is a very common symptom of MS, and it's important that people feel they can get an effective treatment when it's needed. More research is needed to discover whether some anti-depressants are more helpful in MS than others.

So, it was another bumper bundle this month. Does the reporting of research results slow down in the summer? Let you know in July!


  1. "people with MS also experience atrophy (wasting away) of the brain and spinal cord" - this bit is scaring me!

  2. I think everyone gets some atrophy as they get older anyway...and you're on a good treatment now! x

  3. Let's hope so! I wonder if the cognitive problems of MS are due to brain atrophy?