Danny Buckland explains multiple sclerosis in plain language, and outlines treatments on offer and in development
WHAT IS MS?
Multiple sclerosis (MS) is a neurological condition that damages the central nervous system. The body’s immune system attacks and degrades a fatty tissue coating, called myelin, that surrounds and protects the nerve fibres of the brain and spinal cord.
The term refers to the multiple areas of tissue hardening (sclerosis) that disrupt signals from the brain to all parts of the body.
The MS Society sums up the impact by likening the body’s central nervous system to the electrical supply in a home. If the wiring is faulty, lights flicker, the TV jumps channels and computers freeze. In MS, the appliances are different parts of the body that can malfunction causing pain, discomfort and disability.
Relapsing and remitting MS strikes in cycles that can be days, weeks or months apart and, although the patient can make a good recovery, each relapse can take its toll on the myelin sheath. At this stage, MS is an inflammatory condition. Over time, the majority of these patients will reach the progressive phase, which is known as secondary progressive MS, which is dominated by accumulating and irreversible disability. Some 15 per cent of people have progressive disease from the outset.
Although not fatal, it can weaken the immune system and people can die from complications related to MS. Symptoms include mental and physical fatigue, visual problems, difficulties with speech and swallowing, cognitive impairment, balance and co-ordination issues, along with muscle stiffness and pain. No two cases are the same and symptoms can vary in duration and intensity making life unpredictable.
Scientists cannot say with certainty why someone gets MS, but viruses in childhood or adolescence, a lack of vitamin D and smoking have been identified as potential triggers, and the root cause is likely to be a combination of genetic and environmental factors. It is not hereditary, but there is a heightening of risk among family members.
“We do not know for sure what causes MS, but it is a dog that keeps biting in different places at different times,” says Dr Eli Silber, a consultant neurologist and MS specialist at King’s College Hospital, London.
The random nature of its strike pattern makes it difficult for clinicians to target and, although it is manageable, MS has a major, long-term impact on lives.
MS was first described clinically in 1868, but therapy progress was slow until 20 years ago when magnetic resonance imaging (MRI) techniques allowed more accurate and swifter diagnoses, and disease-modifying treatments (DMTs) cut relapses by 30 per cent.
RELAPSE AND REMITTING MS
The lifeline for MS patients has been a suite of disease-modifying treatments (DMTs) taken as tablets or injections, which help neutralise the harmful cells at work during a relapse, and shore up the central nervous system to reduce the level and effect of attacks.
They are not a cure but, combined with symptom management treatments, which deal with a range of symptoms from tiredness to bladder problems, first-line treatments can reduce relapses by up to 50 per cent.
Newer drug therapies can have even better results, but they are harder for patients to get on the NHS as they are given as second-line treatments.
Patients can also boost their defensive arsenal with alternative therapies, such as acupuncture, massage, yoga, meditation and physiotherapy. Vitamin D supplements are recommended by some physicians, but as yet have not been shown to change the course of the disease.
The bleak landscape for MS patients began to change with the introduction of beta interferon in the late-1990s, an injection given every other day that lessened inflammation, although it did have flu-like side effects.
The number and potency of DMTs has continued to grow and among them are Fingolimod (Gilenya), Natalizumab (Tysabri) and Alemtuzumab (Lemtrada).
Gilenya, a daily tablet, works by binding to the surface of white blood cells in the immune system, trapping them in lymph nodes, hampering their ability to attack the central nervous system. It is generally given to patients who have failed on first-line therapies and can cut relapses by more than 50 per cent.
Tysabri, a monoclonal antibody taken as a monthly infusion, sticks to molecules on certain immune cells and stops them getting through the blood-brain barrier. It is a key treatment for more aggressive relapses.
Lemtrada, which was made available in England and Wales on the NHS in April, is given as a course of infusions annually. It kills off the cells in the immune system that mistakenly attack the myelin. When new cells are generated, they are thought to be free from the rogue element. The drug, developed by the University of Cambridge and Genzyme, resulted in far fewer relapses than in study subjects on beta-interferon injections in clinical trials.
Another great encouragement is the discovery that the brain can repair itself in remission by creating new myelin to boosts nerve protection. But the challenge is to accelerate the process for effective relapse damage repair.
MS specialist Dr Eli Silber emphasises the importance of specialist MS nurses in supporting patients with psychological issues.
PRIMARY AND SECONDARY PROGRESSIVE MS
Around 80 per cent of people with relapsing and remitting MS will develop the progressive form of the condition, which is where the neurodegeneration hits a downward trajectory.
There are no licensed treatments for this stage. Disease-modifying treatments (DMTs) have been trialed, but have shown only flickers of hope. The lack of effective treatments has galvanised global action and the Progressive MS Alliance, a collaboration of MS organisations, is connecting scientific programmes and awarding grants to boost research.
“There has been such an explosion of new and exciting anti-relapse DMTs that the scientific and research community can now focus more on progressive MS which we just don’t understand,” says Jeremy Chataway, a consultant neurologist at the Queen’s Square MS Centre, the National Hospital for Neurology and Neurosurgery, University College London. “There is now a global focus to this problem. We first need to slow the progression by putting in repair drugs and re-myelinating.”
Dr Chataway offered recent hope with his phase II interim results on the use of a high dose of a statin, published in The Lancet, which showed a “favourable effect on the rate of brain shrinkage” in patients taking 80mg of simvastatin, double the normal dose used to treat high cholesterol.
“It was very encouraging and exciting. We need further trials, but it is a very good step in the right direction,” he says.
Dr Chataway is running the £2.7-million MS-SMART trial that will evaluate three promising drugs in 440 patients at 15 centres in England and Scotland. The trial, funded by the Medical Research Council and the MS Society, is being run jointly with Professor Siddharthan Chandran at Edinburgh University.
Collaboration between King’s College and Imperial College London is using stem cells to test the potential of Fingolimod and Tysabri on progressive MS.
A small Phase II study by Biogen Idec, published in the journal Neurology, had recorded promise in Tysabri, reducing inflammation in progressive patients.
“A lot of the research has been in the early anti-inflammatory areas of MS,” says MS specialist Dr Eli Silber. “There needs to be more for the degenerative progressive side of the disease where we have been less successful at slowing down the process.”
Professor Chandran, who is pioneering research into how the brain can repair itself, describes progressive MS patients as “the lost tribe of MS” because of the absence of any DMTs for this phase of the disease that ultimately affects the majority of sufferers. “This is the great unmet need but there are some potential wins,” he says.
THE FUTURE OF MS
MS has emerged out of the dark ages and is now a “pathfinder” disease whose research could accelerate treatments for dementia, Parkinson’s disease, Huntington’s and motor neurone disease.
Solutions for the degenerative type of MS could be transferrable across other conditions, says Professor Siddharthan Chandran, director of the Centre for Clinical Brain Sciences and clinical director of the Anne Rowling Regenerative Neurology Clinic, University of Edinburgh.
It was thought that damage to the myelin was irreversible, but studies have shown the brain actually starts laying down new myelin during remission.
“It is nothing to do with doctors, it is a natural event,” says Professor Chandran. “We grew up being taught that, unlike the liver, skin and gut, for example, the brain could not repair itself, so the logic was that following injury you had no ability to repair. However, recent identification of brain stem cells challenges these assumptions.
“An example of brain stem cells in action is the laying down of new myelin which in turn is protective of damaged nerves. The problem is that it does not do it sufficiently, so our challenge is to supplement and enhance it by finding the cues to promote and accelerate brain stem cell mediated repair. The idea would then be to prescribe drugs that will mobilise your own or endogenous brain stem cells to repair the damage caused by MS.
“An alternative approach is to make human brain stem cells in a ‘dish’ in the lab and then parachute these into the injured MS brain. My view is that mobilising our own brain stem cells using drugs is likely to be the future and most cost-effective method to promote repair in MS.”
He adds: “In the next five to ten years, there will be huge advances in therapeutic trials where you are testing drugs predicted to promote the brain’s own capacity to repair itself.
“I don’t want to fuel false hope, but I am optimistic we will make inroads in the medium term which will give us a window into progressive MS as well as other degenerative disease including the dementias.”
The buoyant research field includes more than 6,000 patients being enrolled on clinical trials into progressive MS over the next five years. And an early-stage study at the University of Utah in the United States has shown that treatment with human stem cells can enable mice crippled with a form of MS to walk again.
“Everyone is trying their best to see if we can get a chink of light,” concludes consultant neurologist Dr Jeremy Chataway. “It would be good to have something, even if it’s not much to start with.”