Document Directory

19 Mar 01 - Medicine - New Blood Thinner may be Biggest Advance since Aspirin
14 Mar 01 - Medicine - Scientists defend new therapy for Parkinson's
14 Mar 01 - Medicine - Parkinson's miracle cure turns into a catastrophe

19 Mar 01 - Medicine - New Blood Thinner may be Biggest Advance since Aspirin

Bill Price

Cincinatti Now--Monday 19 March 2001

A blood thinner already used after angioplasty has been shown to be a highly effective treatment for people with chest pain or mild heart attacks, and could potentially prevent 100,000 heart emergencies a year in the United States.

A major study released Monday found that the drug, called Plavix, reduced the risk of death, strokes and new heart attacks in these people by 20 percent, making it probably the most significant advance in their treatment since the introduction of aspirin.

"This is a breakthrough," said Dr. Valentin Fuster of Mount Sinai School of Medicine in New York. "It will change the practice of medicine."

Some 2 million Americans are hospitalized with mild heart attacks and bad chest pain annually. Experts said the drug's impact will be even greater if it becomes routine treatment for the additional 1 million Americans who have full-blown heart attacks.

"Everyone will be put on this," said Dr. Christopher Cannon of Brigham and Women's Hospital in Boston. "It's relatively cheap and has monster benefits. This is what we have all been waiting for."

Heart attack patients are already routinely sent home with aspirin, beta blockers, ACE inhibitors and cholesterol-lowering drugs.

Currently, Plavix, which was introduced in 1998, is given primarily to prevent dangerous blood clots after balloon angioplasty. But doctors say it will soon become a regular pill for many more heart patients.

The study, which was directed by Dr. Salim Yusuf of McMaster University in Hamilton, Ontario, was presented at a meeting in Orlando of the American College of Cardiology. The study was financed by Plavix's makers, Sanofi-Synthelabo and Bristol-Myers Squibb. The study was conducted on 12,562 patients at 482 hospitals in 28 countries. All victims had what doctors call acute coronary syndrome. This is either mild heart attacks -- known technically as non-Q-wave attacks because of their appearance on electrocardiograms -- or unstable angina, which is chest pain that is especially severe or unpredictable.

All patients got their standard treatments, including aspirin, which has a similar effect as Plavix on the clotting cells called platelets. They were randomly assigned to get either daily Plavix or dummy pills within a day of their symptoms and stayed on the drug for periods ranging from three months to a year.

Doctors began to notice a benefit of the drug within the first two hours of treatment. They calculated that after a year, 9.3 percent of patients on Plavix had suffered a stroke, a new heart attack or died of cardiovascular disease, compared with 11.5 percent of those getting standard treatment.

The only important side effect was bleeding, which Plavix triggers about as often as aspirin does. The average patient follow-up was nine months. The study suggests that Plavix could prevent 28 major life-threatening events for every 1,000 patients treated over nine months, Yusuf said. Six patients per 1,000 would need a transfusion for bleeding.

"It's a very exciting result on efficacy and a reassuring result on safety," Yusuf said. If given only to patients with acute coronary syndrome, it will prevent between 50,000 and 100,000 new heart attacks, strokes and cardiovascular deaths in the United States each year, Yusuf estimated.

Worldwide it could prevent 250,000 to 500,000 of these if used on just one-fifth of all patients who might benefit. Plavix has also been linked to thrombotic thrombocytopenic purpura, or TTP, a dangerous and exceedingly rare form of anemia.

Experts estimate that it may occur in 4 of each 1 million patients treated with Plavix, and no cases were seen in this study. Plavix typically costs about $3 a day. Dr. Robert Califf of Duke University estimated that adding Plavix to the list of drugs given to heart-attack patients will increase their daily drug bill by $8 to $10.

A study is under way on 30,000 people in China to see if adding Plavix truly improves the outcome of full-blown heart attacks. It is also being tested on people with heart rhythm abnormalities called atrial fibrillation as a safer alternative for the drug warfarin.

14 Mar 01 - Medicine - Scientists defend new therapy for Parkinson's

By Jeremy Laurance, Health Editor

Independent--Wednesday 14 March 2001

Transplanting brain cells from aborted foetuses into the brains of sufferers from Parkinson's disease may point the way to an effective treatment for the devastating neurological condition, researchers say.

In the first controlled trial of the technique, which involved the controversial use of "sham" surgery, American researchers have shown it brings "some clinical benefit" to younger but not older sufferers.

A cure for Parkinson's disease is still a long way off but reports yesterday that thedevelopment of serious sideeffects in some patients whoreceived the transplanted brain cells spelt "catastrophe" for the research were unduly gloomy, experts said.

Experimental transplants of foetal brain cells into Parkinson's patients have been tried for almost 20 years with mixed results. The technique was pioneered in Sweden and it was used by scientists in Birmingham and elsewhere in Britain in the 1980s and in other countries since. Human and pig foetal cells have been used.

However, progress has been hindered by the difficulty of running a controlled trial to assess the treatment.

Researchers, led by Professor Curt Freed from the University of Colorado, overcame this difficulty by obtaining ethical approval to perform sham brain surgery on half of the 40 patients in their study. The patients were aged 34 to 75 and all had severe Parkinson's, characterised by rigidity of the muscles, difficulty walking and tremor.

The surgery involved drilling four holes in the forehead of each patient and injecting brain tissue from four foetuses, aged six to ten weeks from conception. The patients having sham surgery underwent the same procedure but without the injection of tissue after the holes in the skull had been drilled. A separate group of doctors, not involved in the brain operations, rated the patients before and after surgery.

Tests showed patients aged under 60 improved more than older ones. The benefit was equivalent to about half the effect of the drug levodopa, given for the condition. However, when patients were asked to rate their own progress, all claimed to be improved after surgery and the change was not significantly greater in the transplant group than in those who had the sham surgery.

More than a year after the treatment five patients - 15 per cent of the group - who had initially done well developed serious side-effects, sparking alarm that the treatment may do more harm than good. The side-effects indicated that the transplanted foetal tissue had grown and was producing too much dopamine, the brain chemical that is deficient in Parkinson's sufferers.

One of the researchers, Dr Paul Greene, a neurologist from Columbia University, told The New York Times the sideeffects were tragic and catastrophic. "They chew constantly, their fingers go up and down, their wrists flex anddistend. It was tragic, catastrophic. And we can't selectively turn it off."

He added: "No more foetal transplants. We are absolutely and adamantly convinced that this should be considered for research only."

But the report of the findings in the current issue of The New England Journal of Medicine says research involving new treatments is always risky and treatments are modified in the light of experience. In relation to the side-effects, the authors say: "The simplest response to this outcome would be to transplant less tissue in the future."

An editorial in the journal says: "The brain is a most complex structure so incremental results on the way to cures are to be welcomed rather than dismissed as less than perfect." It adds that the best hope for the future is likely to be the use of stem cells grown from embryos rather than aborted foetuses, the use of which raises practical and ethical difficulties.

Robert Meadowcroft, director of research at the Parkinson's Disease Society, said: "Obviously the results for the patients with serious side-effects are very distressing and we have to learn how to switch the cells off. But it is not all doom and gloom. I think embryonic stem cell research offers more hope for the future."

14 Mar 01 - Medicine - Parkinson's miracle cure turns into a catastrophe

Sarah Boseley, health editor

Guardian--Wednesday 14 March 2001

Hopes of an early cure for Parkinson's disease by the implantation of foetal cells into the brain have been dashed by the devastating results of the first full trial of the technique, which found that a number of the patients were left with tragic side effects which cannot be undone.

The results of the trial will dismay Parkinson's sufferers around the world who had hoped the controversial treatment, which has been available in experimental form since the 1980s, might eventually spell an end to the crippling disease.

The American scientists who conducted the research found the therapy did not benefit patients over the age of 60 at all. Some of the younger patients did improve, but for 15% of those who received the implants, the outcome was worse than the disease.

After a year of apparently doing well, these patients began to writhe, jerk their heads uncontrollably and throw their arms about involuntarily as the foetal brain cells that were intended to produce dopamine, the chemical that is depleted in Parkinson's sufferers, went into overdrive. The cells appear to have grown too well and are producing excessive amounts of the chemical. The scientists have no way bringing the dopamine levels back down.

Paul Greene, a neurologist from the Columbia University College of Physicians and Surgeons in New York, who was one of the researchers, said the results were "absolutely devastating" for the five patients who cannot control their movements.

"They chew constantly, their fingers go up and down, their wrists flex and distend," he told the New York Times. "It was tragic, catastrophic. And we can't selectively turn it off."

One man now has to be fed through a tube because he can no longer eat while another periodically becomes unintelligible during the day when the side effects, which in his case come and go, set in.

Dr Greene says the technique must go back to the laboratory. "No more foetal transplants," he said. "We are absolutely and adamantly convinced that this should be considered for research only. And whether it should be research in people is an open question."

The shocking results of the study are a setback for the scientists who hope that research into stem cells - the basic cells formed by the splitting of a fertilised human egg - may lead to cures for degenerative brain diseases.

While scientists cultivating stem cells will have a much clearer idea of the quality and quantity of the material they have than those using foetal tissue, the theory behind the implantation technique - to "seed" the brain and encourage regeneration - is the same.

The foetal tissue technique has not been used in the UK since an outcry over the use of aborted foetuses put a stop to such research in the 1980s. Brain cells that produce dopamine are extracted from the foetus and cultured. The tissue strands that result are implanted into the areas of the brain that are supposed to produce the chemical.

The US trial was the first to be properly controlled. Forty patients, aged from 34 to 75, were randomly assigned to receive either the foetal cells or nothing. To ensure that the results were due to the treatment and not a placebo effect, all the patients underwent surgery - four holes were drilled in the brain, whether foetal cells were put in or not.

The outcome, reported in the prestigious New England Journal of Medicine, will force a rethink over the treatment.

Gerald Fischbach who was director of the National Institute of Neurological Disorders and Stroke which funded the study, said that this was the first time a technique which some neurosurgeons promoted as miraculous had been thoroughly evaluated.

"Ad hoc reports of spectacular results can always occur," he said. "But if you do these studies systematically, this is the result you get."

The surgery in the study was carried out at the University of Colorado School of Medicine in Denver, while the evaluation was done in New York.

Robert Meadowcroft, director of policy and research at the Parkinson's Disease Society in the UK, said the results were disappointing but did not, in his view, spell the end of any attempt to "seed" the brain with either foetal cells or, in the future, stem cells.

"We need to learn how to switch these cells off once they have done their work," he said.

Within a couple of years, there may be trials of techniques to implant stem cells into the brains of people suffering from degenerative diseases in this country, following the decision by parliament to allow stem cell research.

Martin Edwards, chief executive of ReNeuron, a UK company working on developing stem cell lines for medical treatment, said he believed the problem with using foetal cells was that nobody could be sure how much dopamine-producing tissue was being implanted.

But he said he was convinced that scientists would eventually succeed in helping patients with these distressing brain diseases. "There are some upsides. The cells have survived and a proportion of patients benefited. I interpret this with cautious optimism."