Tuesday, April 24, 2007


A pill that can correct a wide range of faulty genes which cause crippling illnesses should be available within three years, promising a revolution in the treatment of thousands of conditions. The drug, known as PTC124, has already had encouraging results in patients with Duchenne muscular dystrophy and cystic fibrosis. The final phase of clinical trials is to begin this year, and it could be licensed as early as 2009. As well as offering hope of a first effective treatment for two conditions that are at present incurable, the drug has excited scientists because research suggests it should also work against more than 1,800 other genetic illnesses.

PTC124 targets a particular type of mutation that can cause very different symptoms according to the gene that is disrupted. This makes it potentially useful against a range of inherited disorders. The same drug could be given to patients with Duchenne muscular dystrophy, the most serious form of the muscle-wasting condition, cystic fibrosis, which mainly affects the lungs, and haemophilia, in which the blood does not clot. It can be taken orally, and safety trials have not revealed any major side effects. “There are literally thousands of genetic diseases that could benefit from this approach,” Lee Sweeney, of the University of Pennsylvania, who is leading the research, said. “What’s unique about this drug is it doesn’t just target one mutation that causes disease, but a whole class of mutations.”

In most genetic conditions, between 5-15 per cent of cases are caused by a defect called a “nonsense mutation”. Genes are instruction manuals for cells to make proteins, but nonsense mutations in effect introduce a command halfway through that stops production. The kind of protein disrupted determines the nature of the disease. In Duchenne muscular dystrophy, for example, the protein necessary for normal muscle development is not made, and the fatal wasting disease is the result. In haemophilia, it is the gene for the clotting agents factor VIII or factor IX that is disrupted.

PTC124 works by binding to a part of the cell called the ribosome, which translates genetic code into protein, and allows it to ignore nonsense mutations. The gene can be read straight through and a normal protein is produced. The beauty of the drug is that it should be useful with any disease caused by a nonsense mutation, no matter what its outward effects. The error is not corrected, but ignored. Patients would have to take the pill throughout their lives.

PTC124, which is made by PTC Therapeutics, has been staggeringly successful in animal models. A study published today in Nature shows that in mice with a nonsense mutation that causes Duchenne muscular dystrophy, the drug starts dystrophin production and restores their muscles to health. The drug has passed safety trials in humans, and the results of phase-two trials on cystic fibrosis and Duchenne muscular dystrophy will be published shortly. About 13 per cent of patients with Duchenne muscular dystrophy have a nonsense mutation and should respond to the drug. It would not be suitable for treating different mutations in the dystrophin gene, or diseases not caused by nonsense mutations.

Other diseases that can be caused by nonsense mutations include beta thalassaemia, a blood disorder, and Hurler syndrome, in which children’s mental and physical development stops and most patients die by the age of 10.


Pesky genes again: This time for exercise

The Government may be wasting its time encouraging children to spend more time on sport and exercise in an effort to reduce obesity. Research at Peninsula Medical School in Plymouth, reported in today’s times2, suggests that a child’s propensity to be active is genetically determined. Children are said to find their own activity level, regardless of how many opportunities are offered. If the naturally inactive are forced to be more active at school, they do less at home, while the naturally active need no encouragement.

Professor Terence Wilkin, who has carried out trials with young people, says that his research shows that Government programmes to increase levels of activity do not reduce obesity. There are 1.8 million overweight children and 700,000 obese young people in Britain. Rates of obesity more generally have trebled since the 1980s, and the condition is estimated to cost the nation 7 billion in health expenditure. But while active children may be healthier, it remains unproven that inactive ones can be persuaded to do more, Professor Wilkin says. “So far, the evidence is bleak,” he adds.

The claim follows US research last week suggesting that a fat gene can decide whether some people have a propensity to put on weight. Some research has suggested that activity does help. In one study, children who tried a nine-week programme with their parents, which involved a combination of exercise, healthy eating, motivation and positive thinking strategies, were still benefiting from the scheme 12 months later.

The researchers found improvements in the overweight children’s body mass index, waist circumference, fitness, lifestyle and self-esteem following the programme and these were “largely sustained” after a year. “Thirty per cent of UK children are now considered to be obese or overweight — it is an immense public health issue in both immediate and long-term health,” said Professor Alan Lucas, director of the Medical Research Council childhood nutrition research centre at University College London Institute of Child Health.

His “Mend” approach — “mind, exercise, nutrition, do it!” — was adopted by 107 families during the trial but it is now being rolled out across the country. More specifically, a study in Bristol found a link between increased activity alone and obesity, suggesting that an extra quarter of an hour vigorous exercise a day was enough to make a difference. But the problem with these studies is that they do not show if fat children are fat because they are inactive, or inactive because they are fat. If Professor Wilkin is right, efforts to expand school sports may make children fitter, but no thinner.



Just some problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize salt and fat. But we need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. And Eskimos eat huge amounts of fat with no apparent ill-effects. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter and margarine? They are just about pure fat. Surely they should be treated as contraband in kids' lunchboxes! [/sarcasm].

Trans fats:

For one summary of the weak science behind the "trans-fat" hysteria, see here. Trans fats have only a temporary effect on blood chemistry and the evidence of lasting harm from them is dubious. By taking extreme groups in trans fats intake, some weak association with coronary heart disease has at times been shown in some sub-populations but extreme group studies are inherently at risk of confounding with other factors and are intrinsically of little interest to the average person.


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