Yet again, there's been lots of interesting research published this month. Some of it is quite technical, but I'll do my best to translate it into English - depends on me working out what it means myself though!
Epstein-Barr virus, which causes glandular fever (mononucleosis), are more likely to get MS than people without. British researchers looked at the two together, to see if their data could help explain the variance of the disease across the UK. They found that adding the effects of Epstein-Barr and exposure to sunlight together explained more of the differences than exposure to sunlight alone. They suspect that exposure to Epstein-Barr may lead to an abnormal response to vitamin D deficiency.
Still on Epstein-Barr virus: a British research team has been investigating the mechanism which causes the virus to increase MS risk. They were looking at epigenetic changes in DNA. Epigenetic changes are non-genetic changes leading to the genes behaving (expressing themselves) differently. These effects can last for several generation. There is now convincing evidence for an epigenetic component to MS. Effects have been found for mother and child, grandparent and child, and early life (birth month). This study found many locations on the genome different before and after infection with Epstein-Barr.
I've also previously mentioned that people with one autoimmune condition seem more likely to have another, and various pieces of research are being done to confirm this with people with MS. Spanish researchers investigated people with MS to see whether coeliac disease was more common in them than in the general population. Coeliac disease is an autoimmune disease of the small intestine, caused by a reaction to proteins in wheat, barley and rye. Worldwide, about 1-2% of the general population have coeliac disease. This study found that 11% of people with MS had coeliac disease, and a very high prevalence of 32% among their first degree relatives.
Two different research teams, one in the USA and one in Switzerland, have found that an immune system molecule called GM-CSF plays a central role in the inflammation of the central nervous system that occurs in conditions like MS. The research was in animals bred to have a condition that mimics MS. If some way can be found of blocking GM-CSF activity, this would be a possible treatment for MS.
Previous studies have shown that white blood cells called leukocytes enter the central nervous system and play a major part in causing the damage contributing to MS symptoms. Other studies have shown that molecules called MMPs help the leukocytes enter the CNS. Now Canadian researchers have found that a molecular switch called EMMPRIN plays an important part in this process. They found that inhibiting the production of EMMPRIN reduced MS-like symptoms in mice. They also found that EMMPRIN is significantly raised in brain lesions in MS patients. EMMPRIN is another new possible target for MS treatments.
One of the major concerns with MS, and other conditions like it, is uncertainty: not knowing how far, and how fast, disability will progress. Now researchers from the Mayo Clinic in the USA have discovered what they say is a way of predicting how disability will progress in people with secondary progressive MS (SPMS). They found that people with SPMS and a faster disability rate had higher levels of an immune system molecule called immunoglobulin G in their cerebrospinal fluid. They concluded that if someone with SPMS has a higher level of IgG, it is likely that they will have a faster rate of disability.
But do we want to know? Of course, it would be lovely to know we're going to have a slow rate of progression. But there's the risk of learning the opposite...not sure it's a test I would want.
German researchers have now found that the (possibly hormonal) protection of pregnancy is extended if the baby is exclusively breastfed. However, breastfeeding can't be combined with disease-modifying therapies, so previously the mother had to decide without clear evidence to support their choice. More research is needed, though.
So, on to medical treatments. First, some news about an existing treatment, interferon-beta, from a research group in Spain. HHV-6 is a form of the human herpes virus, and is present in a high proportion of the human population. It causes the childhood fever known as exanthem subitum or roseola infantum. Although it then remains in the body for life, it is symptom-free. These researchers found that people with antibodies to HHV-6 in their blood had more relapses and responded less well to interferon-beta than those without.
There has been a lot of media coverage over the UK approval of Gilenya (fingolimod), the first oral disease modifying treatment for MS. This is only one of the many possible links. The media (perhaps understandably, given their general audience) didn't give much stress though to the conditions under which it will be given. I think they're important. Gilenya is for people with aggressive relapsing remitting MS (RRMS), and will only be prescribed when the standard therapies have failed. This is because of possible serious side effects, including reduced heart rate and eye problems. So for most people with RRMS, I'm afraid it's injections as before!
Now onto newer disease modifiers, still in the research stage. Laquinimod is another oral treatment, and has just completed a large phase 3 clinical trial with over 1100 patients in 26 countries. The Italian researchers found that those on laquinimod had 23% fewer relapses, 36% less disability progression, and 33% less brain atrophy than those on a placebo. It seems to be well tolerated and have a good safety rate. A promising treatment, but a pity from a personal viewpoint that yet again it's for people with RRMS!
Another phase 3 clinical trial reporting recently investigated the use of an oral drug called BG-12 (dimethyl fumarate) in more that 1200 people with RRMS. Study participants who were taking BG-12 were significantly less likely to have had a relapse after 2 years than those on a placebo. There was also a significant reduction in the annual relapse rate, the number of new or enlarging brain lesions, and the rate of disability progression. Unfortunately, BG-12 has to be taken 2 or 3 times a day, which could reduce compliance. If a sustained release version can be developed, this could be a really useful treatment for people with RRMS.
Olesoxime is a proposed new treatment for spinal muscular atrophy (SMA), a genetic disease characterised by progressive degeneration of muscle neurones. As MS attacks the same part of the neurone as does SMA, French researchers have been investigating whether olesoxime could also be beneficial in MS. They suspect that while acute relapses are caused by inflammation of the CNS, progression is caused by degeneration. The research has not yet reached human volunteers, but looks promising.
Finally, reports on research into treatment of two symptoms of MS. Ampyra (dalfampridine) is a drug designed to help with mobility problems. It has been approved in the USA and various other countries, but not yet in the UK due to concerns over side effects. Detailed analyses of all the Ampyra trials that have taken place show that there is increased risk of seizures, and also of urinary tract infections - always a concern for people with MS, particularly those on disease modifiers which depress the immune system.
phase 2 clinical trial is beginning on a new drug for neuropathic pain. It's hard to believe that it was as recently as the 1980s when MS pain was acknowledged. Those of us with chronic neuropathic pain know how severe and debilitating it can be, and how badly it can affect quality of life. The trial for the new drug, AVP-923, will measure levels of pain, fatigue, sleep quality and cognition. Sounds very interesting - I look forward to seeing the results!
That's it for May. Another long post I'm afraid, but they will keep doing this interesting research!