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UK: An Answer to Parkinson's? (Filed: 01/06/2004) The Telegraph, UK 'I can be a mum again' Recent research into gene therapy has produced encouraging results, reports Christine Doyle Few professors of neurosurgery would be so confident as to describe the results of recent research as "fabulous". When, however, the professor is Tipu Aziz, consultant neurosurgeon at Radcliffe Infirmary in Oxford, and regarded by the Parkinson's Disease Society as a "key opinion leader", it is safe to assume that he is on to something. The research that excites Aziz was carried out in France and relates to gene therapy. It involves genetically manipulating viruses to produce dopamine, the neurotransmitter that controls smooth movement and is deficient in the brains of Parkinson's sufferers. Parkinson's is a progressive and devastating neurological disorder that can affect all activities, including talking, swallowing, walking and writing. It arises when defective cells in the part of the brain that controls movement die. Why this happens is unclear, but once 80 per cent of the cells have been destroyed, the symptoms emerge. About 120,000 people in Britain are affected, and 10,000 new cases are diagnosed each year. "The manipulated viruses would act as a `repair' rather than simply an alleviation of symptoms in the hope that drugs would become unnecessary," says Aziz. "So far, the research with viruses has been carried out only on animals. Initial results in rats were encouraging, and work last year in monkeys is even more promising fabulous. Basically, normal movement, activity and behaviour were restored. The technique appears to be safe and the monkeys have continued to produce dopamine." The next step is to test the concept in humans, and Aziz is planning an initial trial. "It could start within 18 months, once approval is given by the gene therapy advisory committee," Aziz is due to tell those attending the second in this year's Science Today, Health Tomorrow lectures at the Royal Institution in London on June 16. These lectures, which enable members of the public to question experts about the latest research, are supported by The Daily Telegraph and sponsored by the healthcare company Novartis. In fact, the Oxford trial would not be the first gene therapy trial for Parkinson's. A trial under way in New York involves switching off the hyperactivity of the subthalamic nucleus that drives the Parkinson's symptoms. However, Aziz has reservations. "The technique turns a critical area of the brain from positive to negative. We do not know enough about the brain's neural interactions to know what that will do." At present, drugs that restore levels of dopamine in the brain are the mainstay of Parkinson's treatment. Although they are initially effective, they cause severe side effects in up to 70 per cent of patients. These include confusion and hallucinations. While future drugs might minimise these problems, neurosurgery is increasingly used in the meantime. And thanks to molecular and technological advances over the past 10 years, it is ever more exact. Pallidotomy, for example, which involves burning out tissue in a part of the brain called the globus pallidus to reduce involuntary movement, is less likely to cause side effects than in the past. Fifteen years ago, American researchers showed that the subthalamic nucleus, which had not previously been associated with Parkinson's, was over-active in sufferers. This led to the development of the deep brain stimulation technique. The surgeon implants electrodes in the subthalamic tissue and they are controlled by the patient using an external switch. This technique, pioneered in France, has become a major and at more than £30,000 expensive form of treatment. About one in five patients might benefit, and it can reduce tremor, rigidity and slowness of movement. "Another one in five patients have a related syndrome a kind of `Parkinson's plus' condition and are unable to move properly," says Aziz. "This syndrome is resistant to drugs, so the patients have no break from their excruciating symptoms. We are now working on stimulating the peduncular pontine nucleus, an area deep in the brain, but it could be four years before we can try it in patients." The targeted injection of chemicals nerve growth factors into affected brain tissue is another approach, being researched in Bristol. Inevitably, some therapies have failed to live up to their promise. "Foetal cell transplants did not lead to a dramatic improvement," says Aziz. "The logistics of collection after terminations were horrendous and controversial." An equally controversial alternative is to transplant stem cells developed from embryos used for research and manipulated to produce dopamine. "One drawback is that in animal studies some transplants get out of control and grow tumours deep in the brain. Although the technique offers real hope, we are more than five years from clinical use." 'I can be a mum again' When Ashley Harting was pregnant with her third child, her husband noticed, one night, that her left hand was shaking while she slept. She was 30 at the time, and the shaking continued after the birth of Francesca, who is now 13. "I think most people noticed it well before I was aware of it," says Harting. "I was an educational welfare officer, which involved driving all over the county, and my driving started to get quite erratic. But my GP dismissed my concern. He said, incredibly, that it was my age: I had had three children, so what did I expect? "Then, I had a serious car accident nothing to do with my shaking but my condition deteriorated afterwards. I felt frightened and insisted on being referred to a specialist." The specialist diagnosed writer's cramp. "He suggested I was swinging the lead and wanted time off work. He even tutted while he was talking to me." After a second consultant suggested that she might have multiple sclerosis or Huntingdon's disease, she and her husband split up. "I felt under enormous stress. I was shaking, my speech was slurred, my movements were becoming impaired. Yet another doctor suggested it was all in my head after a while, I began to think it must be true." Harting was 36 when she was finally diagnosed. Shortly after moving back to her home county of Lincolnshire, a GP, who became very supportive, told her she had been seriously misdiagnosed. "Even then, the hospital chaplain asked me, patronisingly, if I was a young person with an old person's disease." In fact, Harting was among the five per cent of Parkinson's sufferers who are diagnosed under the age of 40. She was given a variety of pills and as she was a young patient was treated as a guinea pig, to some extent. "At the time, I was on an average of 40 or 50 pills a day," she says, "and although these helped, my symptoms were hard to control. I was in and out of hospital, seeing a range of specialists. At times, I could scarcely walk, though I was determined to carry on as normally as possible for the sake of the children, who were now without a dad. "Often, I could not cook properly for them or join in their activities. At one point, they had to help me to do everything, even washing and dressing. In the past, I had always talked fast gabbled even but now I was talking slowly and slurring my words and had become a quiet person, my friends tell me." The turning point came when Harting's GP felt she needed more help. She was put on a trial for deep brain stimulation at the National Hospital for Neurology in London. "The stimulator is like a pacemaker and I turn it on from an external control on the left side of my chest, below the collarbone. It was not pleasant having it implanted it took eight hours but I knew it was working straight away. My movements became much smoother, the shaking eased and I began to walk and speak properly. After about six months, I felt completely stable. I am now off all medication." Harting, now 43, stresses she is not cured. "I have problems with urinary incontinence, and try to avoid stress, which makes it worse," she says. "I don't know what will happen in the long term." Linda Kelly, chief executive of the Parkinson's Disease Society and chairman of the Science Today, Health Tomorrow lecture, is not surprised at Harting's delayed diagnosis. "We still hear of doctors who suggest a patient's symptoms are due to alcohol," she says. "We stress the importance of having access to treatment as early as possible, at any age, to slow progression of the disease, prevent depression and enable the patient to live as normally as possible." Harting describes the effect of the brain stimulator as phenomenal. She now cooks, gardens with Francesca and can even drive her elder daughter, Lydia, to college. "My children and my mother were so supportive, never grudging," she says. "Now, I feel like a normal mum again." Parkinson's Disease Society helpline: 0808 800 0303, or see http://www.parkinsons.org.uk For local PDS branches and support groups, tel: 020 7932 1306 SOURCE: The Telegraph, UK http://tinyurl.com/2pw8g * * * ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn