An experimental treatment is transforming MS sufferers by 'outwitting' the disease.
Tuesday 7 May 2002
EIGHTEEN months ago, Melanie Randall-Coles was so disabled, she could do nothing for herself. Today, after trying a new approach to treating MS, she says she feels like she has won the lottery and has "the world in my hands".
"I was totally dependent, like a baby," she says. "At only 25, I thought my career had come to an end. There seemed no future ahead, except to be looked after for the rest of my life."
Melanie, who lives in Leicester, is an occupational therapist at a local hospital and could not be more overjoyed to be back at work full time. Her first symptoms of MS appeared four years ago.
She is one of 50 people in this country who have been prescribed an experimental and extremely powerful drug called Campath-1H, an antibody developed originally to treat a form of chronic leukaemia. It acts on the immune system and has been dramatically successful in reducing the relapse rate in MS patients treated at Addenbrooke's Hospital in Cambridge.
The hospital has been the only one to test the drug's use in MS. The idea is that Campath suppresses immune cells called T Cell lymphocytes. These cells, usually involved in fighting infection, become "wrong footed" in MS and start to attack the body's own tissue. They react to antigens in the fatty insulation - the myelin sheath - around nerves in the brain and spinal cord, and treat them as if they were foreign tissues.
If these immune system "offenders" can be suppressed for long enough - which does not leave the patients vulnerable to unusual infections - the hope is that they will be "re-educated". When they come back into service, they will be much less likely to resume the mugging attacks on the central nervous system.
So far, these patients have not taken part in specific trials, but each has been assessed individually by the Addenbrooke's neurological team, led by Professor Alastair Compston and Dr Alasdair Coles, a Wellcome Advanced Fellow. Now the team is ready to move on. The researchers are co-ordinating a trial about to start at Addenbrooke's and at centres in Bristol, Liverpool and Newcastle. The first of 180 new patients are being recruited.
The challenge, says Dr Coles, is to find out if early treatment with Campath - within five years of the first symptoms appearing - will prevent the underlying progression of the disease. Those on the trial will randomly be assigned to either Campath or beta interferon. The latter also suppresses the immune system and the Government recently agreed that it should be more widely available on the NHS.
Dr Coles is optimistic: "The trial will take a long time, but I believe we are moving from the orthodox view of waiting for people to go downhill before starting to do something. While studying the first patients who were given the drug, we learnt a lot more about MS. Now we want to study people who are fit and well and have had MS less than five years."
Next Wednesday, in "The Challenge of Multiple Sclerosis" - the third in the current Science Today Health Tomorrow series of Royal Institution lectures - he will argue that "we need to do something urgently to secure the future for more people with MS". The Daily Telegraph, the Royal College of Physicians, the Patients Association and such charities as the Multiple Sclerosis Trust support the lectures. Novartis Pharmaceuticals sponsors the lectures, which give the public and Daily Telegraph readers a rare chance to question the experts directly.
Melanie was just 23 when she had the first inkling of the ordeal ahead: "I had optical neuritis: it was like a blurry cloud across my right eye. My fiancé was a doctor, so we realised it might be an MS symptom." A brain scan confirmed their suspicion and Melanie was given steroids to calm down the relatively mild attack.
But the eye trouble flared again and was followed during the next year by numbness in her right leg. "I am very stubborn and refused to use a stick. I used to 'furniture walk', hand over hand." Next, her right hand went "dead". She had four severe attacks in 1999, each time taking more than a month to recover. Surgery in January 2000 at Addenbrooke's to remove a lump, disclosed during her brain scan, triggered a massive flare-up of MS.
"Fortunately, the lump was benign," she says. "But although I was warned I might have a relapse after the operation, I was not prepared for how awful it would be. We had to postpone our wedding." Her fiance, Dr Vivan Talwar, was a lifeline. "He was wonderful: he would get me up, dress me, wash me under the shower while I sat on a seat, prepare breakfast. All this was so exhausting, I would have to sleep for two hours. Then Talwar would be back at lunchtime to help again. I felt completely powerless."
Gradually she improved. Her local authority would not fund beta interferon, but she and her fiance had inquired extensively about the latest MS research and heard about Campath. Prof Compston agreed to prescribe it on a compassionate basis. "I think he felt I was the type of MS patient who might benefit in the long term."
The drug is given intravenously over five days for four hours a day, with a follow-up treatment at 18 months. There can be severe side effects and Melanie says she was anxious before the treatment. "I had a horrible rash, but - despite the misery - I knew straight away that I was getting better. By the time I left hospital, I already felt like a new person.
"Within a few months, I was transformed from somebody who had nothing to someone with a future. We went ahead with the wedding."
One major side effect of the drug is that in 30 per cent of cases, including Melanie's, it can trigger a hyperthyroid condition called Graves disease. This suggests that similar regulatory cells in the immune system are thrown off balance by the treatment. However, Melanie concludes: "Taking tablets to correct this is a small price to pay to be back at work, a healthy woman again. It all seems like a miracle."
Melanie is having regular scans to monitor any fresh inflammatory attack to her brain cells. She has had one mild relapse and a second infusion of the drug 12 months later. With Campath, she has a 95 per cent chance of a reduction in relapses, against 70 per cent with beta interferon. The critical question, however, is whether the experimental drug will prevent secondary degeneration - the slippery slope to irreversible disability.
Dr Coles says: "We are beginning to think of MS as rather like two diseases. This is a new concept in MS. It is exciting that Campath can reduce the attack rate more powerfully than any other drug. However, at least half of the patients tested so far at Addenbrooke's already had disease progression, despite the reduction in relapses.
"Even when beta interferon is given early, we know that after five years a significant proportion have progressive deterioration. These are very early days with the new trial. It could take a number of years for the final answers. Our hypothesis is that Campath might halt or delay progression. Now we have to find out."
'Disgrace' to NHS
Paola De Marco, 34, a Scottish-born Italian, runs a fast food pizza and burger outlet in Olney, Bucks, with his wife, Tracey. Doctors diagnosed him with multiple sclerosis at the age of 22. Six years ago, he was desperate to prevent relapses and perhaps delay long-term progression, but his health authority would not fund beta interferon.
So Paola decided to pay for the drug himself. But with identical twin boys on the way he could afford only one dose a week at an annual cost of £3,250. "I had fewer relapses, but a few years ago, the specialist told me I had moved to a new stage of the disease. Perhaps I should have paid for three doses a week of beta interferon. But I could not afford them."
On "compassionate grounds" Addenbrooke's has given him Campath. "Already, after five weeks, I am improving. My hope is to be strong enough to exercise and rebuild weak muscles. I don't want to live life in a bubble."
Many MS specialists say the story of beta interferon, which after many years campaigning is to be made more readily available, is a disgrace to the NHS. In America and some parts of Europe, doctors prescribe it at the first signs of MS. That is far from the case yet in Britain.
When the body turns against itself
Multiple sclerosis is the commonest disease of the central nervous system and affects about 85,000 people in Britain - two thirds of them women. It is an auto-immune condition: the immune system reacts destructively to antigens in the protective myelin sheath around nerves as if they were "foreign" tissues. Blurred or double vision, bladder and bowel problems, weakness and exhaustion, poor co-ordination, tingling, numbness and itching are among the early symptoms. At its worst, MS leads to severe disability, as experienced by Melanie.
Researchers believe that, as with many other diseases, there is an interplay of a number of genetic susceptibilities and unknown environmental influences, such as a virus.
Types of MS
Relapsing/remitting Experienced by about two sufferers in three, with, on average, one or two relapses a year of unpredictable severity.
Secondary progressive Many with the relapsing/remitting condition go on to develop a more progressive form of MS, which also varies in severity.
Primary progressive In a small number of people, the disease progresses rapidly from the outset.
Benign About one in 10 have only occasional relapses and little disability.
As part of our Health Tomorrow series there will be a lecture on Multiple Sclerosis on Wednesday 15th May 2002.
Multiple Sclerosis Trust: 01462 476700 http://www.mstrust.org.uk
Multiple Sclerosis Society: 0808 800 8000 http://www.mssociety.org.uk
Campath trial recruitment: Dr Alasdair Coles, Department of Neurology, Addenbrooke's Hospital, Hills Road, Cambridge. CB2 2QQ
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