Pierre Sokoloff and colleagues at the Centre Paul Broca believe they have uncovered a highly promising path for tackling dyskinesia. They tried out three compounds that, like dopamine attach to the D3 receptor and act rather like valves, opening up or reducing the amount of L-dopa that is admitted into the cell. The three molecules, called BP897, ST198 and nafadotride, were tested on five macaque monkeys whose dopamine cells had been destroyed and which were displaying dyskinesia after a prolonged treatment with L-dopa. When used in combination, these "partial agonist" drugs were able to eliminate dyskiniesia yet not lose the beneficial effects of L-dopa.

SNIFFING OUT LUNG CANCER

PARIS

University of Rome scientists have pioneered an electronic nose that they say may one day give an early warning to people with lung cancer. The experimental device works in the same way as hi-tech hygiene "sniffers" already in use the food industry, which analyze air on the production line for the tell-tale chemicals released by rotting ingredients.

    In the case of lung cancer, the e-nose responds to a signature cocktail of alkanes and derivatives of benzene exhaled by someone with the disease, New Scientist reported. The eight-sensor nose proved to be 100-percent accurate in a test at a Rome hospital in which it analyzed a breath sample from 35 people with a large lung tumor and 25 who were healthy.

    The next step is to boost its sensitivity so that it can detect tumors at a much earlier stage. It could be used in routine checkups to screen smokers and other high-risk groups.

    The sensors are made of quartz crystal coated with metal-containing dyes called metalloporphyrins, which bind to specific carbon-based chemicals. The binding very slightly changes the weight of the crystal, causing it to vibrate at a different frequency. A complex gas sample will thus create a unique profile of vibrations from an array of crystals, providing the "signature" of the disease.

SUBTLE FLAW

PARIS

A severe form of diabetes that affects millions of people and a thyroid condition called Graves's disease have been pinpointed to part of a key gene. A subtle flaw in this gene could play the leading role in unleashing these two ailments and a third disease of the endocrinal system called autoimmune hypothyroidism, researchers report in Nature.

    In this new research, scientists put their finger on a stretch of DNA variations, called polymorphisms, on a gene called CTLA4, located on chromosome 2 of the genetic code.

CYBER HUMAN With the help of new scanning and computer technologies, medical imaging technology now show real-time activities inside the human body. Among the recent innovations is 4-D Image System's "Cyber Human," which Dr. Naoki Suzuki, professor of the Jikei University School of Medicine, unveiled early this month at the National Museum of Emerging Science and Innovation in Tokyo.

    CTLA4 is a big player in the immune system. It acts as a molecular control on the T lymphocyte blood cells, which are alerted by antibodies to swarm out into the bloodstream and gobble up viral or bacterial invaders. So if this "brake" is faulty, the T lymphocytes can run amok.

    Small but significant variations in the gene were found in hundreds of families with a history of type 1 diabetes, Graves's disease, and autoimmune hypothyroidism. The results mirrored those among mice that had been genetically modified to have type 1diabetes.

    About 50 percent of the population have this variant, so it is possible that there are other genetic culprits. Several other important genes are activated during the complex molecular ballet involving the "killer" T cells.

    CTLA4 will join a small but fast-growing list of about 10 inherited diseases where a specific gene or-even more accurately, as here-part of a gene has been convincingly established as the culprit.

    Lead researcher Prof. John Todd of the University of Cambridge, however, sounded a loud note of caution: "This is a basic research finding and there's no test that's going to be developed in the near future, no pharmaceutical gold that's going to come out in the near future. This tells us something fundamental about the cause of these diseases. But that's far removed from any immediate impact on or any benefit for a patient."

    About five percent of western populations have autoimmune disorders, a category of ailments that includes rheumatoid arthritis, Addison's disease, and Crohn's disease. These diseases are complex, and environmental as well as genetic factors are involved. One theory is stress, pregnancy, exposure to a microorganism or a drug, or other triggers, could initiate the changes among people who are genetically susceptible.

    Graves's disease affects 0.5 percent of individuals in the western world. It results from an antibody attack on the thyroid, provoking excess hormone secretion and causing tiredness, weight loss, and heart flutter. It is, however, easily manageable.

    Autoimmunite hypothyroidism, which affects 1.0 percent of western populations, is caused by T-cell attacks on the thyroid tissues, leading to deficiency in thryroid hormones.

    In type 1 diabetes, which has a frequency of 0.4 percent in western nations, insulin-producing beta cells in the pancreas are wrecked by autoimmune response. It strikes children instantly and makes them insulin-dependent for life.

OBESITY-CANCER CONNECTION

WASHINGTON

Encouraging Americans to shed their excess weight could prevent some 90,000 cancer deaths a year, according to a study published in the New England Journal of Medicine. The 16-year study of 900,000 men and women for the American Cancer Society (ACS) showed that excess weight and obesity accounted for 14 percent of all cancer deaths in men and 20 percent in women.

    The study focused on 404,576 men and 495,477 women, of whom 57,145 died of cancer. The researchers found that the heaviest members of the group were those with the highest risk of dying of cancer, showing that weight played a greater role in cancer formation than previously known.

    "Overweight and obesity [have] a very broad impact on cancer across most cancer sites," said Eugenia Calle, director of analytic epidemiology at the ACS and lead author of the study.

    Some 65 percent of the adult US population was overweight or obese in 2000, according to the Centers for Disease Control and Prevention.

GENE LINKED TO COLORECTAL CANCER

WASHINGTON

Analysis of the human genome has enabled scientists to draw up a list of genetic mutations linked to over 30 percent of colorectal cancer cases, according to a study in Science.

    Researchers at the Johns Hopkins Kimmel Cancer Center and the Howard Hughes Medical Institute studied 182 cases of human colon cancer to identify mutations in the tyrosine kinase (TK) gene family. TK genes are thought to be good therapeutic targets for managing cancer because the proteins they encode play key roles in controlling cell growth and differentiation.

    The researchers concentrated on the 138 TK genes normally found in humans, and identified mutations in 14 cases linked to colon cancer cases. Scientists knew of the possibility of such mutation, but until now no study had shown the frequency with which this mutation occurs in people suffering from a certain type of cancer, according to study leader Dr. Victor Velculescu.

    "Our findings open the door to individualized analysis and treatment of colorectal cancer," he said. "With this new work one could imagine personalized therapeutics, based on mutations in different kinase genes and designed to match the mutated TK pathways present in each patient's particular tumor DNA."

    Fellow researcher Sanford Markowitz said the research combined two new technological breakthroughs. "The availability of the human genome sequence allows scientists to scan sequences to identify kinases, and the increased speed with which DNA can be sequenced enables us to rapidly search for mutations in those kinases in human cancers," he said.

VIRUS TO KILL TUMORS

WASHINGTON

Researchers have produced a genetically modified virus that targets and eliminates brain tumors, according to a study at the University of Texas M.D. Anderson Cancer Center. The study successfully tested "viral smart bomb therapy" known as Delta-24-RGD, with no ill effects seen in surrounding healthy cells.

    This represents the first time a successful treatment has been found for malignant glioma, the most deadly form of brain cancer, which currently is incurable, researchers said. The technique uses a therapeutic virus that can spread, wavelike, throughout a tumor, infecting and killing cancer cells, said the researchers led by Prof. Juan Fueyo of Anderson's neuro-oncology department.

    The replication-competent oncolytic adenovirus therapy used "is designed in such a way that it can replicate only in cancer cells, not healthy tissue, to reproduce itself while killing the host cancer cell." "We believe this therapy has a lot of potential," said Fueyo, noting, however, that more study was needed.

    Experiments found more than half of mice that had human glioblastoma tumors implanted in their brains lived for more than four months after Delta-24-RGD treatment, compared with three weeks for untreated mice, the authors said.

    Results of the study, published in the Journal of the National Cancer Institute, are believed to be so promising that the research center is to finance the development of treatment using the technique. The treatment, using an adenovirus related to the virus that causes the common cold, will be tested in humans by the end of 2004.