MS Research Roundup September 2011

Again, a short research review this month. My apologies.

First, an extremely interesting and important genetic study, that has received a lot of media attention. Researchers looked at more than 10,000 people with MS from 15 countries, as well as more than 17,000 healthy controls. We already knew about more than 20 gene differerences that may contribute to people getting MS. The large numbers involved in this study allowed them to find another 29 genetic variants that could contribute.

About half of all the gene variants known to be involved affect the immune system, and one-third have been implicated in other auto-immune diseases, such as Crohn's disease, coeliac disease, rheumatoid arthritis, lupus, and type 1 diabetes.Knowing which genes are involved in MS could potentially help new treatments be developed, including the possibility that treatments already in use for one auto-immune condition could be used for another.

I've mentioned the common herpes virus HHV-6 before. It causes the childhood infection roseola, marked by a chest rash and high fever. However very little is known about it, including how it manages to reach the brain to be implicated in causing conditions like MS, encephalitis and a form of epilepsy.

These American researchers found high levels of HHV-6 in the olfactory bulb (a part of the brain associated with smelling) and in nasal mucus, in over half of their samples. They also discovered that specialised cells connecting the nose to the brain are susceptible to infection by the virus. As ever, more research needed. It could be that infection entering the brain via the nose causes a different disease result from infection entering by another source. This is a really interesting study though.

It's well-known that MS, as well as other auto-immune diseases like lupus and rheumatoid arthritis, are considerably more likely to attack women than men, but it's never been clear why. Now American researchers have discovered a new type of immune system B cell: these make antibodies, which go on to bind to and attack the body's own tissues.

The researchers found higher levels of these cells in elderly female mice, young and old mice prone to auto-immune disease, and humans with auto-immune diseases. They are now seeking a way to treat these diseases by blocking production of the cells.

A very big MS-related story at the moment is vitamin D exposure. A group of American researchers compared vitamin D exposure between childhood (whether the individual had been given cod liver oil) and disease onset (sun exposure in the previous winter) with how rapidly they were progressing.

They found a close link between a low level of vitamin D exposure before disease onset and slower disease progression. They were working only with people with progressive MS, and with quite a small group, so research is needed with a larger group and with people with the relapsing remitting form as well to see if the same results are seen. A really worthwhile and interesting study though.

Daclizumab (Zenapax) is a monoclonal antibody, currently going through trials. In this recent global trial, where daclizumab was injected every four weeks, it reduced relapse rates by around half compared to taking a placebo. There was however an increased risk of infections. Daclizumab is now in phase 3 trials, where it's being compared with beta interferon 1a.

Finally, news on two treatments for MS symptoms. First, the Irish Medicines Board has given approval to the use of Botox for urinary incontinence for MS following the biggest ever clinical trial of Botox for neurogenic overactivity of the detrusor muscle. The study demonstrated that treatment was effective within a couple of weeks and lasted for 8-10 months.

Botox is already in use in the UK, and this large study just confirms its utility. It's an important step towards gaining licences in those countries where it's not yet used.

Many of us with MS, diabetes or shingles know the terrible, ongoing problem caused by nerve pain. Current drugs may not help at all. Now British researchers have discovered that a gene called HCN2 is involved in causing the excessive "firing" of pain-sensitive nerves.

In experiments with mice genetically modified to have the gene removed, disabling the gene was found to relieve chronic and inflammatory pain, but without reducing reactions to acute pain, the type caused by a sudden injury. This is crucial: responses to injuries can be vital to our survival. The researchers hope that they'll be able to develop a drug to block the protein produced by HCN2, so the same effect can be seen in humans.

That concludes this month's research review. Again, apologies for the limited number of items covered, but I hope you'll agree there are some really interesting studies in there.

See you next month!

The right model for killing yourself

"Martin" is 46 and has locked in syndrome He's asking the courts to clarify the law so that doctors and other medical staff who might help him end his life would not  be prosecuted.

This is an extension of Debbie Purdy's case, from two years ago. Purdy successfully argued in court that it was a breach of her human rights not to know if her husband would be prosecuted for assisting her suicide if he accompanied her to a clinic in a country where assisted suicide is legal.

"Martin's" case extends this to doctors and other medical staff, rather than lay-people. His wife has accepted his decision, but does not feel able to assist him.

At least 10% of suicides in the UK are by people with a chronic or terminal illness, and coroners believe that people are increasingly killing themselves at a younger age rather than wait until they are in severe pain. Some coroners avoid probing into what they suspect might be a case of assisted suicide, to avoid causing problems for those left behind.

So why do all these people with long-term illnesses feel that the appropriate response to their circumstances is to kill themselves? (Either with or without help). Opinions, inevitably, differ.

Some argue that the decision is made because the condition - the illness, the disability, whatever - has become too much to bear. Others say that these feelings are often because the individual has not had the chance to live as independent a life as possible within society at large.

The individual's condition on one side and society on the other. That sounds very familiar. And yes, it's our old friends the medical and social models of disability again.

Which is more important in an someone's decision whether they want to live or die?  The way their physical disability affects them as an individual, or how easy it is for disabled people to be part of mainstream society?

Just to be upfront, I have no intention (in the foreseeable future) of seeking assisted suicide. But as I've told you in a couple of posts recently, I've been having major problems getting out because of physical problems. At the moment, the accessibility or otherwise of society is kind of irrelevant to me, and my physical impairments are totally primary. At other times, or for other people, the physical problems may be secondary to accessibility, housing problems or employment discrimination.

So overall, I think sometimes the medical model is the right one and sometimes the social model. Or, at least, there's a continuum. At one end is "pure" medical model thinking, at the other end is "pure" social model thinking. Most of us are somewhere in the middle, and we move back and forward along the continuum depending on circumstances. (It's made of nice slidey material. Makes it easy.)

The vast majority of us could never kill ourselves, in any circumstances. And if someone is considering it, whether that decision is rational or irrational is a whole other packet of Jaffa cakes. For those few who have decided to seek assisted suicide though, reasons differ. And that fact must be acknowledged by the disability community.

Not going out

For the last couple of months, I've been having real problems in getting out. Not because of agoraphobia: I'd love to get out. Because of physical difficulties, and complete and utter lack of spoons. I just haven't had the energy to go out.

I used to be - well, not exactly a party animal (though I've had my moments!), but I went out a fair bit. Part of it was day-to-day getting out, of the going-to-the-shops, paying-the-bills type. And of course work, back when I was still able. In these teched-up days, the internet offers alternatives to much of that kind of going out, for those who want them.

But part of it was the joyous, wonderful kind of going out: meeting your mates, going to the pub, going to gigs. Falling in love with the band who were supporting the one you'd actually gone to see. Your table in the pub laughing so loudly that the landlord has to ask you to quieten down. An evening at the fair, throwing balls at coconuts to win teddy bears.

It's that kind of going out I miss so much. I have wonderful friends I'm in contact with online, by text or by phone: but it's just not the same as when I meet up with them in real life.

And even the boring, everyday kind of going out means you're still part of the community at large. You're still "normal" (whatever the hell that means!) rather than stuck permanently indoors.

So I'm still hoping I'll beat these damn recurrent infections, and get enough energy back to do some going out again. Because this not going out is really getting me down.

Revolting disabled people

Over the last week, we have all been horrified by the scenes of violence and criminality shown in Tottenham, Ealing, Hackney, Croydon in the London area, as well as further afield in England, in cities including Manchester, Birmingham, Nottingham and Bristol.

Those responsible are now being arrested and dealt with through the justice system. Everyone, and his dog in many cases, has spouted forth his or her opinion of the causes of the rioting. One factor frequently cited by the chattering classes (much like myself, you might say. And probably rightly) is the alienation of young people, and of the "underclass" that has developed under this and other governments, brought to a head by the savage programme of cuts introduced since the last General Election.

This may be true. The official inquiry into the causes of the rioting might look at such things - I hope so.

But there are other groups, equally alienated by their treatment by successive governments, and equally if not more affected by government cuts. Why weren't they out there rioting, looting, and setting fire to things?

They? I mean us. Disabled people.

Yes, things are better than they were in relation to accessibility, job opportunities and so on, but they're not improving nearly fast enough. Disability hate crime is still a regular occurrence and not taken nearly seriously enough. And we're facing frightening, ideologically motivated cuts to our benefits. Why shouldn't we be out there rioting?

Well, first of all, there's the practicalities of the matter. Few of the shops being looted looked very wheelchair accessible - through the windows at least. And wouldn't the glass puncture the tyres? For those of us who have disabilities that are also illnesses, it's difficult to do anything spontaneous like that. And what about if you need a PA to get out?

Then there's the age profile of the rioters. Overwhelmingly, those charged with riot-related offences are young, about 3/4 being under 25. Disabled people, on the other hand, tend to be older than the general population: although of course there are disabled children and young people, many disabilities only come on with age, so the number of disabled people in the population increases with age. With age comes...well, let's call it wisdom. Or maybe it's apathy. Something like that, anyway.

I think all of us, even living in our own homes rather than in care or nursing homes, undergo a kind of "institutionalisation" - to be placid and well-behaved little crips. It's hard to break out of that, to fight against it either physically or with your words.

This, along with the physical and logistic problems, is why it was such an impressive achievement when thousands of disabled people participated in the Hardest Hit march in May, protesting against cuts to disability benefits and services. It's a real shame that their strength and commitment got so little media coverage, in comparison to that given to a few trouble-making idiots on the TUC March For The Alternative.

So. Why weren't disabled people rioting? Some of the rioters probably were disabled of course, as not all disabilities are visible...but in general?

For most of us, I imagine it's because, the same as me, we know what's right and what's not. In other cases, it's just too damn difficult! Maybe some people don't feel national politics affect them?

A whole range of reasons, then. Just like there's a whole range of disabled people. And probably, like there's a whole range of reasons for what the rioters did.

Damn. Wouldn't it have been easy if there was one nice easy knee-jerk cause and solution?

"I'm better"

For the last month or so, I've really not been well. A succession of UTIs, along with the increase in MS symptoms they bring with them. Antibiotics would stop the symptoms of the infection during the course: but then, soon after, it would return.

Then, at the stage when my wee looked like creosote and smelt like something had died in it, I could barely stand, and was really just hoping I would die quickly...I discovered (/my doctor prescribed) nitrofurantoin. This seems to be the latest thing for persistent UTIs, as a friend has just been given it for the same thing. And you know the best thing? It works. Well, so far at least.

So, it seems I no longer have a UTI. I'm better.

Better.

What does that word mean to someone with a long-term illness? I'm never going to be really "better". I have a progressive condition. I'll always have dreadful fatigue. I'll always have cognitive impairment, and all my other symptoms. I can take tablets or injections to help with some things, or work around them, but they're always going to be there.

It seems to me we redefine what "better" means, for us, in our personal circumstances. I'm better because my UTI has gone away: in terms of my symptoms, I'm less worse.

Similarly, we redefine the words describing how we are. I can say "Yeah I'm good", even though I'm in pain and exhausted, because for me, in my terms of reference, that's good.

So...yeah, I'm better. Which is great!

MS research roundup August 2011

First this month, I have to apologise for the complete lack of posts since the last roundup. I've been a bit MSified - and in the less bad bits, I've been attempting to do some "real work". I have told myself off severely, and promise I will blog more this month. Honest.

My poorliness in July also meant that I wasn't keeping my usual eagle eye on what research results were being reported. Sorry and all for the low number of results I discuss in this post.

So on to the research...and more evidence for a link between MS and current vitamin D levels. British researchers compared average vitamin D levels among people in Scotland with MS, and their admission to hospital for things like relapses and infections. They found that the two factors were linked: hospital admissions were highest in spring (April-June) when vitamin D levels were lowest.

This suggests that vitamin D levels are associated with whatever it is that causes people with MS to be admitted to hospital. We already know that vitamin D affects the immune system: being deficient can increase the risk of infections and probably relapses.

Australian researchers have found that past infection with Epstein-Barr virus (EBV), the virus which causes glandular fever (mononucleosis) can combine with genetic variations to increase the risk of developing MS by up to 20 times. There was no evidence that a current infection with EBV could bring on MS.

Not research, but a discussion...a group of researchers held a session on cognitive (thinking) dysfunction in MS, and the problems of developing longitudinal tests and standardising data for the effects of MS on the mind. The researchers gave the contrasting example of Alzheimer's disease: the cognitive decline caused by that disease is faster and more certain than in MS, where cognitive decline affects about 6% of patients each year.

As far back as 2002, researchers published a consensus paper agreeing a battery of tests to be used to measure cognitive decline in people with MS. According to this discussion, it is time to update the consensus to 2011 standards.

Disappointingly for those of us who have followed its progress, the UK National Institute for Health and Clinical Excellence (NICE) has issued a draft recommendation that Gilenya (fingolimod) should not be prescribed on the NHS. This is because NICE feel that it has not been trialled against the correct drugs: it has been compared with a placebo and with Avonex, while NICE argue that it should be compared with other beta interferons as well as Avonex, and with Tysabri.

Gilenya is licensed for adults with highly active relapsing-remitting MS, who have had either one relapse in a year despite being treated with beta interferons, or two disabling relapses regardless of their treatment. The evidence Novartis submitted to NICE mainly dealt with a subset of the first of these two groups.

People with MS, healthcare professionals and others are invited to comment on this decision. However, it really sounds to me like the ball is in Novartis's court, to submit further trial evidence.

One interesting study that reported recently was carried out by an international group of researchers. They found that health-related quality of life, depression, fatigue and thinking all improved when people took Gilenya. However again the comparison was with a placebo, not with an existing treatment.

Finally for this month, exciting news of an upcoming major stem cell trial. British researchers plan to collect participants' own stem cells from their bone marrow, grow them in the laboratory, then reinject them into their blood. The cells will then make their way to the brain where it is hoped they will repair the damage done by MS.

The research is part-funded by the MS Society, which is concerned by the availability of unproven stem cell treatments. At present, there are no proven stem cell treatments, but many people with MS have been attracted to overseas stem cell clinics offering expensive "cures".

So, that's it for this month. See you in September!

MS research roundup July 2011

First this month, a very exciting discovery (for researchers and science geeks like me, anyway). Until now, MS researchers working in the very early stages of a project, when animals must be used, had only been able to use non-human primates when the illness had been artificially induced. Now a naturally occurring disease in Japanese macaques has been found by researchers in America.

This can give many more clues about the causes and development of the disease. It has already been discovered that the condition is associated with a herpes virus - linking in with previous research suggesting that MS in humans may be linked to previous infection with the herpes strain Epstein-Barr virus, which causes glandular fever (mononucleosis).

More herpes news. A Taiwanese research group have found that there may be an increased risk of MS in the year following an attack of shingles, caused by the herpes zoster virus, which also causes chickenpox. The study followed very large groups of people with and without shingles, and found that those with were almost 4 times as likely to develop MS as those without. This is a very interesting study, well designed and with a very large sample group: however it was limited almost entirely to Chinese patients, and Asian populations have considerably lower rates of MS than Western. This work needs to be repeated on other ethnic groups.

Now a piece of research that may not be news to many of us (including me!). American researchers have discovered that fatigue is the first symptom of MS in nearly 30% of cases, often months or even years before any demyelination can be observed. I can certainly remember multiple visits to my GP complaining of fatigue, when I was either told "But everyone gets tired." ("No this isn't NORMAL tired!") or offered anti-depressants. Not particularly helpful.

The group is planning studies to see if unexplained fatigue can be used as a predictor of MS, and another to see if people whose first MS symptom is fatigue differ in any other way from those who have multiple MS-related symptoms.

It's been known for some time that women with MS who become pregnant have a higher than normal likelihood of experiencing a remission during pregnancy, and then experiencing a relapse after the birth. Now Canadian researchers have looked at the effect of MS on the actual pregnancy. They found overall that pregnancy was safe for women with MS, with no significant difference in gestational age, birth weight or type of birth (vaginal or caesarian).

Women with a greater level of disability were more likely to have adverse birth outcomes, but these did not reach statistically significant levels. The researchers also found that women with MS were more likely to be overweight, which is associated with greater risk during pregnancy and birth.

Now, on to treatments, and first some news about existing drugs. I've spoken before about the highly promising treatment Tysabri.  Getting Tysabri carries the risk of developing the rare but severe condition progressive multifocal leukoencephalopathy (PML). PML is more likely if you have previous been exposed to (and therefore have antibodies to) anti-JC virus (JCV).

From now on, all patients in the EU will be tested for JCV antibody status before starting on Tysabri, and JCV antibody status will be included as a risk factor in Tysabri labelling. The risk of PML is still there, but it should be greatly reduced if people with antibodies to JCV do not take the drug.

Another existing treatment, of longer standing, is Copaxone(glatimer acetate). A group of Canadian researchers found that after a year patients receiving a new oral drug, teriflunomide, along with Copaxone, had only about 1/3 the number of lesions of a control group who took Copaxone plus a placebo tablet.

Teriflunomide has previously been tested with interferon: that trial also showed impressive results. It operates by stopping certain immune cells from dividing. This sounds like a very promising adjunct treatment. I hope it's trialled in larger groups, and against other therapies, as soon as possible.

American researchers have developed a very promising new approach to identifying the "self" proteins our bodies attack in auto-immune diseases like MS, rheumatoid arthritis and diabetes. Their new technique, called phage immunoprecipitation sequencing, allows the identification of any interaction between an autoantibody in the cerebrospinal fluid and the self-protein that drives the autoimmune response. This work is at very early stages, but could eventually be developed into diagnostic tests and even treatments.

Meanwhile, British researchers have discovered a synthetic chemical compound which both reduces the inflammatory response in the body and stimulates the body to produce interferon-beta, an anti-inflammatory molecule commonly given to people with MS. Together, these effects cause significant reduction of inflammation in an animal model of MS. The researchers also found that immune system cells from people with MS were more sensitive to the drug than immune system cells from people without the condition.

Excitingly, a joint research group from Britain and the USA have discovered a new molecule that they believe may lead to a drug able to repair myelin by stimulating stem cells. Again, this is very early stage research. Hopefully it will move to clinical trials and ultimately to some form of treatment, probably within 10-15 years. That would repay all the work that's being going on in myelin repair research.

So, that's what happened in June. Some really exciting news this time! See you, same place next month?