Saturday, January 19, 2008

"Unprecedented" results after new Alzheimer's treatment

A bit too good to be true but interesting

In findings described as "dramatic and unprecedented," researchers say they have found an injection treatment that leads to marked, sustained improvements in Alzheimer's disease symptoms. The study's lead author owns stock in a company that could profit from the findings, and the scientists acknowledged that other biases could have colored the results. Nonetheless, the improvements in patients with the notoriously intractable, memory-erasing illness were tested, widely noticed and are "worthy of further investigation," they wrote in a paper on their results.

Drawing of a crosssection of a typical healthy brain (above) compared to an Alzheimer'saffected brain (below). (Courtesy U.S. Nat'l Inst. on Aging)

The findings are of "significant scientific interest," added Sue Griffin, another Alzheimer's researcher. She is coeditor-in-chief of the Journal of Neuroinflammation, which published the study online Jan. 9.

More than five million Americans have the devastating, fatal brain disease, according to the Alzheimer's Association. The few effective treatments known generally do little more than delay its progression. By contrast, the new therapy, using a drug already approved to treat other illnesses, would seem to reverse key Alzheimer's symptoms within minutes -- though scientists aren't speaking of a "cure" because the treatment isn't expected to hold off the effects forever.

The study, from the University of California, Los Angeles and University of Southern California, focused on a molecule called tumor necrosis factor-alpha, or TNFalpha, a critical component of the brain's immune system. Normally, the molecule fine-tunes the transmission of electrical signals in the brain. But excesses of it seem to disrupt this regulatory process in Alzheimer's, the researchers said. They explored the effects of reducing levels of the molecule through injections of a drug called etanercept. The lead author, Edward Tobinick of UCLA, owns stock in Amgen, the company that makes the drug.

Within minutes of a spinal injection of etanercept (trade name Enbrel), molecules of the drug latch onto the TNFalpha protein, causing it to stop working, the researchers said. Etanercept is approved by the U.S. Food and Drug Administration to treat certain immune-related disorders.

There has already been considerable buzz around the use of anti-TNF therapeutics for various diseases; the new findings justify some of that excitement, the researchers said. Griffin discussed the results and their implications in a commentary in the journal alongside the research paper.

Although the paper itself focuses on only one patient, scientists said others with mild-to-severe Alzheimer's have also gotten the treatment. There was "sustained and marked improvement" in each case, according to an announcement of the findings from the University of Arkansas for Medical Sciences, where Griffin conducts research. The statement also called the results "dramatic and unprecedented."

The study's authors said some biases could have crept into the outcomes. "All participants, including the examining physicians, were aware of the treatment," they wrote in the paper, which focused on an 81-year-old doctor sick with Alzheimer's. This awareness could "bias the results, and a placebo effect cannot be ruled out." The placebo effect occurs when patients feel better simply thanks to knowing they've been treated.

However, family members, friends and objective tests all attested to considerable improvements in the patient's memory, they wrote. He went from not being able to state the date, day of the week, year, place, city, or state, to being able to give the day of the week, month, and state, California. The improvements lasted for at least seven weeks with weekly treatment, wrote Tobinick and his research colleague, Hyman Gross of the University of Southern California.

However, they noted, only some of Alzheimer's effects are likely to be reversible, as structural damage to brain cells eventually sets in for which there is no known cure.

Nonetheless, "it is unprecedented that we can see cognitive and behavioral improvement in a patient with established dementia within minutes" of treatment, Griffin said in the University of Arkansas annnouncement. "It is imperative that the medical and scientific communities immediately undertake to further investigate and characterize the physiological mechanisms involved. This gives all of us in Alzheimer's research a tremendous new clue about new avenues of research, which is so exciting and so needed."


Leukaemia hopes

Identical twin sisters have led British scientists to a breakthrough in leukaemia research that promises more effective therapies with fewer harmful side-effects. By comparing Olivia Murphy, 4, who is in remission from acute lymphoblastic leukaemia, and her healthy sister, Isabella, researchers have traced the tumour stem cells that drive the most common form of childhood cancer. The discovery will enable doctors to screen young leukaemia patients to establish the severity of their illness and spare some the harrowing side effects of aggressive chemotherapy.

Olivia, from Bromley, southeast London, is a prime example of how hazardous this can be: although her treatment has been successful, it left her unable to fight off a chicken pox infection that blinded her in one eye. Chemotherapy has such harsh effects on children with leukaemia that between 1 and 2 per cent die because of the drug regime, according to Philip Ancliff, the consultant who treated Olivia at Great Ormond Street Hospital in London.

The stem-cell advance, from a team led by Tariq Enver, of the University of Oxford, and Mel Greaves, of the Institute of Cancer Research in London, will also open new approaches to treating the disease more effectively. It should allow the scientists to develop ways of targeting the stem cells that drive the blood cancer and cause relapses, so that patients can be cured. This form of the disease accounts for about 85 per cent of the 450 childhood leukaemias diagnosed in Britain each year.

The study, published in Science, could have further implications for the cancers that cause lung and colon tumours, as these are also thought to be propagated by rogue stem cells. Another application could be preventive treatment for children like Isabella who are known to be at high risk of acute lymphoblastic leukaemia, whose “pre-leukaemic” cells could be killed before they cause any damage.

Professor Enver said: “This research means that we can now test whether the treatment of acute lymphoblastic leukaemia in children can be correlated with either the disappearance or persistence of the leukaemia stem cell. Our next goal is to target both the pre-leukaemic stem cell and the cancer stem cell itself with new or existing drugs to cure leukaemia while avoiding the debilitating and often harmful side effects of current treatments.”

Professor Greaves said: “This study of a twin pair discordant for leukaemia has identified the critical stem cells that initiate the disease and maintain it in a covert state for several years. We suspect that these cells can escape conventional chemotherapy and cause relapse during or after treatment. These are the cells that dictate disease course and provide the bullseye to target with new therapies.”

The twins have been crucial to the new research, as they are genetically identical but one has developed cancer whereas the other has not. The scientists found that the girls’ blood contains genetically abnormal cells known as pre-leukaemic cells. These were formed by a mutation known as translocation, in which two genes fuse to create an abnormal new one. This random event happened in a single cell in one of the twins — it is impossible to tell which one — while they were still in the womb. As the twins shared a placenta, the original mutant’s daughter cells populated the blood of both sisters.

Analysis of Isabella’s blood suggests that about one in 1,000 of her lymphocyte blood cells is preleukaemic. About 1 per cent of these pre-leukaemic cells are also stem cells that can start and sustain the cancer. As Isabella is still healthy, it is clear that the translocation cannot trigger leukaemia by itself. About one in 100 children has the translocation, but only one in 100 develops cancer. “The crucial question is in which cells does this start,” Professor Enver said. “What is the critical hit? Isabella gave us an opportunity almost to look back in time, to see which cells the cancer begins in.”

They did this by comparing the twins’ blood. In Olivia, but not in Isabella, some pre-leukaemic stem cells had acquired a second genetic mutation that turned them cancerous. This could have begun in a single cell, possibly because of an infection.

The discovery will help doctors to monitor Isabella, and children like her, so that further genetic damage in her pre-leukaemic stem cells is caught early. Her risk of acute lymphoblastic leukaemia is estimated at one in ten, compared with one in 10,000 among children with no family history. It will fall with every year that she remains healthy. By the time she is 14, her pre-leukaemic stem cells should have died naturally. “Pre-leukaemic cells are still evident, so the sword of Damocles is still hanging there,” Dr Ancliff said. “Hopefully, we will see them disappear.”

The study also identifies precisely the cancerous stem cells that propagate the cancer. This should enable doctors to adjust the strength of chemotherapy to match a child’s condition. As cancer stem cells can survive conventional chemotherapy, the research could also help scientists to design drugs that kill cancers.



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].

9). And how odd it is that we never hear of the huge American study which showed that women who eat lots of veggies have an INCREASED risk of stomach cancer? So the official recommendation to eat five lots of veggies every day might just be creating lots of cancer for the future! It's as plausible (i.e. not very) as all the other dietary "wisdom" we read about fat etc.

10). And will "this generation of Western children be the first in history to lead shorter lives than their parents did"? This is another anti-fat scare that emanates from a much-cited editorial in a prominent medical journal that said so. Yet this editorial offered no statistical basis for its opinion -- an opinion that flies directly in the face of the available evidence.

Even statistical correlations far stronger than anything found in medical research may disappear if more data is used. A remarkable example from Sociology:
"The modern literature on hate crimes began with a remarkable 1933 book by Arthur Raper titled The Tragedy of Lynching. Raper assembled data on the number of lynchings each year in the South and on the price of an acre's yield of cotton. He calculated the correlation coefficient between the two series at -0.532. In other words, when the economy was doing well, the number of lynchings was lower.... In 2001, Donald Green, Laurence McFalls, and Jennifer Smith published a paper that demolished the alleged connection between economic conditions and lynchings in Raper's data. Raper had the misfortune of stopping his analysis in 1929. After the Great Depression hit, the price of cotton plummeted and economic conditions deteriorated, yet lynchings continued to fall. The correlation disappeared altogether when more years of data were added."
So we must be sure to base our conclusions on ALL the data. But in medical research, data selectivity and the "overlooking" of discordant research findings is epidemic.

"What we should be doing is monitoring children from birth so we can detect any deviations from the norm at an early stage and action can be taken". Who said that? Joe Stalin? Adolf Hitler? Orwell's "Big Brother"? The Spanish Inquisition? Generalissimo Francisco Franco Bahamonde? None of those. It was Dr Colin Waine, chairman of Britain's National Obesity Forum. What a fine fellow!


No comments: