Health Meaning

The researchers used a modified AIDS virus to stop a devastating brain disease in two young boys. The treatment, in which the virus has issued a therapeutic gene is the first time gene therapy has been used successfully against adrenoleukodystrophy X-linked (ALD) - a disorder that is always fatal if untreated. With this proof of principle, scientists hope versions of the AIDS virus designed to carry different genes can now be applied to a variety of other diseases.

ALD is caused by a defect in a gene on the X chromosome that produces a protein called ALD. Cells need this transporter protein to break down certain fats; without it, the fats accumulate and damage the myelin sheath that protects nerves. In X-linked ALD, which strikes mainly boys, patients develop neurological symptoms such as seizures and vision loss around 6 to 8 years, and in a few months, they become paralyzed, deaf, and eventually die. In the 1980s, the parents of a boy with ALD developed a fatty acid mixture they called Lorenzo's oil that may have delayed the disease in their son (and inspired a 1992 film). But the only way to ward widely accepted ALD is a bone marrow transplant, which is risky - 20% to 30% of patients die or have serious complications -. And works best if the donor marrow comes from a brother

Seeking an alternative, pediatrician Patrick Aubourg of INSERM in Paris, the French biomedical research agency, and the University of Paris -Descartes and collaborators in France and Germany tried gene therapy on two 7 years with ALD who could not be associated with a bone marrow donor. They removed the child's blood cells and cells treated with a so-called lentiviral vector, a modified HIV virus carrying the gene for the enzyme they lacked. The virus could not replicate, but it stitched the gene into the DNA of blood cells.

To provide the cells treated room to enter and multiply, the researchers destroyed each bone marrow of patients with chemotherapy. Then they infused the repaired cells in the patient, the cells began to turn the crank on the ALD protein. The idea was that after a few months, some of these cells could migrate in the brain.

As expected, the parts of the brain of patients who have already shown signs of myelin damage initially worsened after gene therapy, because the modified cells will migrate into the brain immediately. But after 14 to 16 months, the blood cells of the boys were still making ALD, and brain images showed that the disease had stabilized or improved, suggesting the protein was produced there. One boy did worse on a nonverbal IQ test, and the other has lost vision, but their scores on verbal tests did not drop as they do in patients not receiving therapy. The results were similar to a bone marrow transplant, the researchers report tomorrow Science .

"There is a real milestone in the field," says neurologist Florian Eichler of Massachusetts General Hospital in Boston. However, it warns that the treatment should not be attempted until the patient has signs of ALD. This is because many boys with the defective gene do not develop the brain disease, and therefore they should not be subjected to such harsh treatment regimen.

the study is also important because it suggests that a lentiviral vector can be safer than other viruses used for gene therapy, gene therapy, says researcher David Williams of Harvard Medical School and Boston children's Hospital . in the best known example, another viral vector cured 20 patients with "bubble boy" immune disease, but it caused leukemia in several of them by inserting its DNA near a gene cancer . An analysis of blood cells of ALD patients suggested that the lentiviral vector is less likely to land in the wrong place. Williams expected that lentiviral vectors will now be used to treat other genetic diseases that involve blood cells, such as sickle cell disease.

A new group adds its voice to the rage on the influence of drug money on research and medical practice, saying it should be more money to study the problem. In a letter sent today to the National Institutes of Director Francis Collins Health, 100 doctors, medical ethicists, and others call for funding:

The recent disclosure of items ghostwritten, physician payments, and use of the doctrine leaders to increase markets for FDA-regulated products indicate that ethical failures can soak biomedical research. ...

In your role as director of "the steward of medical and behavioral research for the Nation," we ask that you acknowledge the standard of research on the effects of conflicts of interests and commercial influence on medical decision making ...

between bench and bedside is a treacherous path with ethical dilemmas. NIH is the best place to launch and support a rigorous scientific investigation into the ethical state of research, the relations of the academic industry, and the effect of this relationship on human health. There are currently no identifiable mechanism through which NIH would fund this research.

The message we want more money for our research seems selfish, and it's not like anything NIH funding in this area already. (For example, NIH Grant supported university surveys financing industry.) But the doctor Georgetown University Adriane Fugh-Berman, who heads a group called Pharmed Out who led the letter says NIH tends to reject grant applications on topics such as ghostwriting and industry funding for medical education. "I think the NIH thought this not from their area, and the problem is that it is not within the domain of person," she said.

signatories of the letter shows that the diversity of voices and came to rule on the matter. The list includes psychiatrists, current and former editors of journals, ethicists (including Lisa Bero of the University of California, San Francisco, who studies the influence of drug money on research), for patients and consumer advocates, medical students, and Susan Wood, FDA official who left to meddle in science by the Bush administration. Pharmed Out is funded by a 04 legal settlement involving the marketing of a Pfizer drug.

The letter asking for a meeting face-to-face with Collins. Stay tuned.

A House of Representatives hearing to examine the science behind a controversial policy on mammography yesterday erupted in a donnybrook.

Conservative members of the Energy Subcommittee and Commerce Health pounced on recommendations to cut back on mammography issued November 16 by the Preventive Services Task Force of the United States a health group appointed by the government councilors, as an example of the bad things that would happen if the current health reform plans moving forward. The Working Group indicated that healthy women should not start routine mammograms until age 50 (the previous council was to begin at 40). Even then, he said, mammograms should be performed every two years as opposed to every year. The working group also recommended that doctors not teach healthy women do regular breast self-exams. The reason in both cases: the aggressive screening tends to produce a psychological unnecessary stress, biopsies and surgery-night that outweigh the benefits for younger women

Representative Joe Barton (R-TX) blasted retirement aggressive working group. screening as a kind of "rationing" -a step Medical along "the path of socialized medicine in this country." Barton and others argued that the working group was trying to reduce medical costs and his new board would cause some women to die. Republican members of the subcommittee also said the new board was a taste of what the health care reform bill House-passed would bring, if adopted. Representative John Dingell (D-MI), a funder of the project of the health reform law, retorted that he was surprised to hear these "fairy tales. ... It's like listening to the Brothers Grimm. "Dingell deplored" the fear tactics. "And then the experts spoke.

The working-group leaders key witnesses Diana Petitti, a biomedical informatics expert at Arizona State University, Tempe, and Ned Calonge, chief medical officer at the Colorado Department of Health in Denver have been scattered questions about why their group had decided to reverse the earlier advice on mammography. (A 02 task force, with different members, recommended annual mammography beginning at age 40) and Petitti Calonge said the decision to deemphasize mammography based on a new review of the best and most recent evidence. Some members of Congress pressed them to recognize that the working group had a goal to reduce unreported medical costs. Both denied. "Cost was not a factor in our considerations," said Petitti. She and Calogne conceded they could have done better in a couple of ways, however. They said that the court did not fully involve the "stakeholders" in its review and recommendations have been poorly formulated Rather than discourage mammography for women in their 40s, what they meant, according to their testimony, was: ".. The decision to have mammograms for women in their 40s should be based on a discussion between a woman and her doctor "

Otis Brawley, a breast cancer specialist and chief medical officer of the American cancer Society, said ACS disagreed with the recommendation that regular mammograms delayed until the age of 50 an ACS panel reviewed the evidence in 07 and reached a different conclusion, he said the women earn more than they lose if they start mammograms at age 40. "experts can look at the science and disagreement" Brawley said. But he approved the conclusion of the working group within self-exams monthly produce too many false alarms and unnecessary biopsies. instead, ACS recommends "breast awareness", an approach that encourages women to be alert to physical changes, but not to the rigorous search for them.

An unscientific delivered what may have been the strongest critic of the day. Fran Visco, a lawyer, a survivor of breast cancer for 22 years, and president of the National Breast Cancer Coalition, called for less emotion and more reason. She said her organization supported the working group and its scientific approach. She added that there is nothing new about the furor it caused

Many of the audience were shocked by the changes in breast cancer screening guidelines but these guidelines and this controversy is not new. ... A National Institutes of Health consensus panel came to similar conclusions in 1997. In fact, historically, scientific evidence did not support the methods of breast cancer screening that have been promoted vigorously in our country . Today we have more evidence and understanding of breast cancer, but it seems that once again, the emotion and the conventional wisdom prevail over science, evidence and progress. Because a health message has been given over and over again and has become ingrained in the public consciousness does not make it okay. ... Too many times ... beliefs seized when there was actually no real evidence behind, and these actions caused harm to women.

Two other witnesses Donna Sweet of the American College of Physicians and Jennifer Luray Susan G. Komen for the Cure foundation, a group of patient advocacy, offered support for the group work but are concerned about the public reaction. Sweet said her organization recommends that women between 40 an 49 years consult their doctor and make an individual decision about mammography. Luray said that "there is enough uncertainty about the age at which mammography should begin and the frequency of screening that we do not want to see a change in policy for screening mammography at this time."

Subcommittee Chair Frank Pallone (D-NJ) ended the session by saying he had hoped to examine the evidence behind the conclusions of the working group, but that the whole issue had become " totally politicized ". He apologized "on behalf of the Congress."

Humans are the best friend of the influenza virus. We give a home. We travel and introduce it to new people. We also provide the nasty invaders with hundreds of our own proteins to help get into our cells and copy itself, as a new study Nature and two in Cell show. While this may seem bad news for us, researchers hope that a better understanding of how we aid and abet the enemy make the virus easier to stop.

Together the three studies map the complex interactions between viral and host genes, a feat achieved for some other viruses to date. But this is just a first draft, and the results of different laboratories are both illuminating and confusing. "The three studies are fantastic," said Sumit Chanda, a systems biologist at the Burnham Institute for Medical Research in San Diego, California, who led a team that published one of the reports online December 21 in Nature . "but everyone brings weaknesses and strengths to the table."

the three laboratories identified several hundred human genes that the flu turns to his advantage, but in the most cases, the groups each hit on different ones: Only about 30 genes overlap, a result that is "very surprising," said Peter Palese, a virologist at the Mount Sinai School of Medicine in New York, who co-authored the paper with Chanda. the two related studies that have appeared online December 17 in cell were led by Stephen Elledge at Brigham and Women's hospital in Boston and Sagi Nir Hacohen Shapira and the Broad Institute in Cambridge , Massachusetts.

Yet even these divergent findings open the door to attack the influenza virus by targeting host proteins rather than the unwanted visitor himself. Current antiviral drugs against influenza, such as Tamiflu, cripple essential proteins of the virus itself, but the flu often develop resistance to them. A better strategy would be to focus on how human cells offer the flu a comfortable home. "It would be very difficult for the virus to develop resistance against a therapy that targets a cell protein," says Palese.

But the first researchers must identify the most important proteins and sort the differences between the three groups. Elledge and Chanda teams used the same basic technique to identify important human genes. They mixed the viruses with human cells, then off human genes one at a time with what is called RNA interference. This revealed specific contributors to the welfare of the flu. They now share their raw data, hoping to adjust how their different experimental conditions have led to conflicting results.

the third study, conducted by Shapira and Hacohen Broad, used a completely different strategy, analysis of the interactions between human and viral proteins, and the levels of different expression genes. This "multi-layer" approach provides more of a big-picture look at the host-pathogen dance the finer-grained results of RNA interference studies.

One of the most intriguing discoveries came out of a choice in the laboratory Elledge hunting for human proteins that interfere with the replication of influenza virus, as opposed those who help him. Elledge, who worked with Abraham Brass Massachusetts General Hospital in Boston, found a whole family of these, called interferon-inducible transmembrane proteins. These IFITMs exist in many other species, and Elledge suggests removing from chicken embryos or animal cells that are used to make vaccines against the flu can greatly boost vaccine production by allowing the virus to be more copies of itself. Comparing the levels of these IFITMs in different people may also explain why some people are more susceptible to influenza virus

Memo flu: .. You are not a friend, and your benefits may be about to expire

A long-standing feud between drug companies and the German institute that evaluates the effectiveness of treatments medical could cost the institute director of his work. Although the post is supposed to be apolitical, members of the new German coalition government called for Peter Sawicki, founding director of the Institute for Quality and efficiency of health care (known by its German acronym IQWiG pronounced ICK-vig), be replaced with someone who is more favorable to the pharmaceutical industry. The Board of Directors of the Institute of Directors should decide on 20 January whether Sawicki, a researcher and expert clinical diabetes, will be replaced when his contract runs later this year.

Sawicki Supporters say the move would endanger the reputation of the Institute for the impartial and rigorous science, and earlier this month a petition signed by 0 clinical doctors and researchers have asked the minister Health and advice on keeping Sawicki. Gerd Antes, director of the German Cochrane Centre in Freiburg, a nonprofit organization that analyzes the effects of health care, said that replacing Sawicki significantly undermine IQWiG and its work. Antes considers anti-Sawicki push "part of the political game to soften and weaken rigorous procedures for new drugs and medical devices in Germany."

IQWiG, based in Cologne, was launched in 04 as part of a reform of the German health care system. With a function similar to that of the National Institute for Health and Clinical Excellence (NICE) in the UK, IQWiG reports inform the panel that decides which treatments are covered by insurance schemes funded from Germany. Sawicki clashed with pharmaceutical companies on access to their unpublished studies and reports of the Institute, as one who has found "no evidence" that a new product has exceeded the oldest synthetic human insulin. Industry groups, especially the German organization of pharmaceutical companies focused on research, VFA, have been very critical of IQWiG, saying, for example, IQWiG is too selective in the choice of studies to include in its assessments.

Big pharma attacks even came from abroad. In March 09, the Research and Manufacturers of America Pharmaceutical petitioned the Obama administration to put Germany on a "priority watch list" trade and intellectual property mainly because of the influence of IQWiG on the market German drug. the petition complained that the Institute "insufficiently taken into account the value of innovative pharmaceuticals," among other complaints. the Obama administration has refused to put Germany on its watch list.

Sawicki acknowledges that it is difficult for new drugs or techniques to make the grade "We introduced a method based on relevant patient outcomes. morbidity, mortality and quality of life," says -it while avoiding what he calls "invalid surrogate mothers," such as cholesterol levels or bone density. "You can reduce cholesterol and increased mortality. You can reduce blood pressure and increase heart failure," he said. Second, he said, "we are looking for . progress "rather than efficiency, which means that innovation is not compared with placebo, but with the current standard of care" We try to answer the question: "is it better" Sawicki said he has some sympathy for drug manufacturers: "It is very difficult to produce something better than what we already had. "

industry complaints about the institute found some support among German politicians. In the October agreement forming new coalition government in Germany, the parties stated their intention to examine IQWiG methods in order to "increase the acceptance of the findings of the institute among patients, caregivers and producers." at the end of November, the German media reported that a white Paper distributed among health policy makers have called for replacing Sawicki and for the institute to be more favorable to industry. Sawicki is also facing an ethics investigation, which he said he asked after a new CFO has found irregularities in expense accounts. News survey, implying have several hundred euros in travel expenses ( see update below ) fled when the white paper was distributed.

the work of the Institute is bound to be controversial, said Antes. Similar research in the US has also drawn criticism. Although the term Sawicki was not flawless, Antes said, he was instrumental in obtaining the institute and running. "He never gives. It has a very strong spine. In 5 years, they have established an institute with a very good international reputation."

UPDATE

Survey Details ethics surrounding spending Sawicki was disclosed in view of Wednesday's decision. the investigators found that Sawicki booked business class tickets for domestic flights and incorrectly claimed over € 1,100 worth of private costs, the most it has since repaid. According to Handelsblatt (in German), which obtained a copy of the confidential report, Sawicki also rented an Audi Q7 in 06 and Audi Q5 in 09 that official cars, although it has agreed to use his private car for business and receive compensation. Handelsblatt reports that investigators found, however, that Sawicki had the tacit approval of the lease, in part to compensate a pay cut that Sawicki known when he took the position of director.

Anticipating a series of federal recommendations on gene patents coming out tomorrow, a former senator and four biotechnology companies and leaders biotech trade groups criticized the Department of Health and Human services (HHS) for decision, they said, a stand that would undermine the objectives of technology transfer the Bayh-Dole Act and the industry biotechnology in general in the United States.

on the basis of project proposals, provided the Secretary of HHS Advisory Committee on Genetics, Health and Society (SACGHS) to be issued six recommendations. The first is the most controversial, suggesting that Congress should pass legislation to exempt patents on genes potentially counterfeit responsibility for anyone to use a gene patent.

This worries biotechnology companies because, as James Davis, Executive Vice President Human Genome Sciences noted, genetic patents generally cover much more than the ACGT nucleic acid sequence in a gene. The patents also relate to proteins produced by the gene, antibodies to proteins and other downstream products of the gene. Without protection for these parts, companies have no incentive to invest in research, Davis argues, and he and others feared the recommendation would find a sympathetic ear in Congress.

The other five recommendations-for example, that companies be required to disclose more trade secrets, or that the US Patent and Trademark Office received consulting receive less attention more technical cadres, who were joined by the Biotechnology Industry Organization (BIO). But leaders have criticized the five other points too expensive.

Although SACGHS recommendations are limited to gene patents, most biotech critics have accused the proposals strike at the heart of the 1980 Act Bayh-Dole, which universities helped commercialize discoveries and move the market. Before Bayh-Dole, the potentially useful products often languished. Former Senator Birch Bayh, co-author of the act, joined the leaders in their criticism today, calling the recommendations SACGHS an attempt "to re-impose the policies that have failed in the past, policies that do not work all just not. "

Jon Soderstrom, official permission to head of technology at Yale University, echoed this comment, saying, "What scares me is that [the recommendations] reconstruct the world as that it existed before 1980. "

coincidentally, the HHS recommendations are appearing at the same time a federal court in New York is hearing an important case, ACLU v. Myriad, if genes patents violate the Constitution. Myriad holds patents on two key genes of breast cancer.

SAN DIEGO -It's an awesome video. An old man in thick glasses and a blue shirt is sitting in a wheelchair. A therapist sits in front of him, off camera. She tries to make him say he is thirsty, but can not produce the words. There are many years man has had a stroke that damaged the part of his brain that allows him to speak, a condition known as aphasia name.

Then slowly things start to change. The therapist begins to hum a simple melody, haunting: two notes at the same height, a third a little higher up, then down. "I thi-i-rsty," she sings. Resting his hand on the table, she taps the hand of man in time, encouraging him to sing. "I'm thirsty," he sings in harmony . She sings the phrase; he sings back. She says the sentence. He says it back. How about on a hot day like today, she asks. "I am thirst ," he says. Within minutes, a stroke patient who was unable to speak for years has learned to express a basic human need.

The patient is Melodic Intonation therapy course. the technique was developed because many patients who can not speak can still sing. Gottfried Schlaug, a neurologist at Harvard University, is studying how and why this treatment seems to work for many patients failed to other forms of speech therapy. It is running a randomized clinical trial of the therapy and so far it looks pretty good find. He spoke during ' a session yesterday on the language of music interactions in the brain at the annual meeting of the American Association for the advancement of Science (which publishes Science NOW).

the race of the patients had damage to part of the left side of their brains involved in language. But similar areas on the right side of the brain may also be used, if the treatment can reach. Making music rotates on a large part of the brain at a time. It urges the skills hearing, emotion, and motor. "Singing can give entry into a broken system by engaging the right hemisphere," says Schlaug. He compared the brain images of patients before and after therapy and found that the right side of the brain changes, both structurally and functionally.

and patients also change. in another video, a man tries to give his address. he fights, but he can not get the words. it is clearly frustrated . It is 4 years after stroke, and man has tried many treatments, all the talk in vain. Then, in a second video taken after 75 therapy sessions Melodic Intonation, man recites his number home, street, and city.

Schlaug think therapy is not widely used in part because many people are embarrassed to sing. "therapists might have a problem to sing with a patient ' he said. And not just therapists. "Most of our male patients have a problem with that." But they install, and therapy itself is easy, he said. "Our next goal is to teach patients caregivers."

Why a person feel more pain than others? Where in the body does HIV hide to escape the treatments? Lauren Schenkman talk about these stories and more with Science podcast host Robert Frederick.

Listen to the Science NOW podcast.

(or listen to the full science podcast.)

Despite its horrific history of causing birth defects, thalidomide has recently made a comeback as a treatment for diseases such as multiple myeloma cancer. Now, a new study suggests that the drug may also relieve symptoms of a genetic disease called hereditary hemorrhagic telangiectasia, a discovery that could help researchers to new therapies for VRL and other vascular diseases.

In the late 1950s and early 1960s, doctors prescribed thalidomide as an anti-nausea drug for pregnant women with a regularity that proved tragic. More than 10,000 children in 46 countries were born with missing limbs and other defects before thalidomide manufacturers have pulled from the market. Researchers have recently begun to understand how the drug made its damage. They know little about one of the benefits of the drug Thalidomide appears to control angiogenesis, the growth of new blood vessels. This property makes it a powerful weapon against some cancers, but scientists do not know how it works.

In HHT, blood vessels grow without the right support cells to maintain stable and solid. Patients have leaking vessels and are subject to potentially fatal bleeding in the brain, lungs, liver and gastrointestinal tract. People with the rare hereditary disease also have frequent nosebleeds, as much as seven a day, which can become so severe that patients require skin grafts in their nose or even more desperate measures to lead a normal life. "Patients VRL get their nostrils sewn just so they can walk down the street," says Christine Mummery, a developmental biologist at the Medical Center of the University of Leiden in the Netherlands.

The addiction thalidomide for targeting blood vessels in tumors is Mummery ask whether the drug's effect on angiogenesis could help people with HHT. When they gave thalidomide seven HHT patients, six had significantly fewer nosebleeds in the month of their first dose, Mummery and his colleagues report online today in Nature Medicine .

to find the mechanism underlying the improvement of patients, researchers tested the drug on mice high to have HHT symptoms. They found that although high doses of thalidomide stop angiogenesis, lower doses actually strengthen blood vessels by stimulating cell growth. Thalidomide seems to pair with a growth factor called PDGF-B to produce more smooth muscle cells that repair defects walled container.

The evidence suggests that the drug works the same way in humans. A nasal biopsy seventh participant (which also saw an improvement, but had to abandon the study because of nerve damage caused by thalidomide) showed layers of smooth muscle cells more than were present in samples from untreated HHT patients. The findings offer new insight about how thalidomide which affects the blood vessels, says Mummery.

They also offer people with HHT hope for more effective therapies in the future, said Paul Oh, an experimental geneticist at the University of Florida, Gainesville, who was not involved in the study. "It is possible thalidomide help with all aspects of HHT," he said. "This is the first major treatment of HHT community works."

The study could well point the way to a more alternative safe, says Rosemary Akhurst, a molecular biologist at the University of California, San Francisco. "ultimately, we do not want anyone to be using a dangerous drug thalidomide," she said. "This can we help take the positive aspects and leave the negative. "

The line most widely used human embryonic stem cells can again be studied with federal dollars. Yesterday, the National Institutes of Health (NIH) has approved four stem cell lines submitted by WiCell, the nonprofit associated with the University of Wisconsin, Madison. The lines include H9, which has been used in more than 500 published studies.

These four lines have been approved under the policy on stem cells in the Bush era, but they had to undergo further monitoring to ensure they meet the rigid rules of ethics issued the last summer the Obama administration. WiCell did not submit requests for lines until two weeks ago. Meanwhile, researchers using H9 worried they might have to cancel research projects. (Researchers had already grants may continue to use the lines of the Bush era, but new grants based on them were waiting.)

The hold-up is because the four lines obtained from embryos that were given to Israel. Collection of documents there and Hebrew translation into English took time, WiCell said in a press release. NIH also added nine lines to the register yesterday by The Washington Post , bringing the total to 64.