A FERTILE GROUND Research into spermatogonial-derived stem cells redefines the expression, "source of life"
WASHINGTON US scientists have discovered how the gene mutation responsible for fragile X syndrome-the most common inherited form of mental retardation-alters the way brain cells communicate, according to a study in the Proceedings of the National Academy of Sciences. In neurons cultured from laboratory rats, the scientists were also able to reverse the effects of the mutation using a drug targeted to the specific site in an upstream pathway of the defect. The finding could lead to the development of human therapies for this previously untreatable condition, the study said. The research was led by Stephen Warren, chair of human genetics at the Emory University School of Medicine, and Gary Bassell, Emory professor of cell biology. "We have now explained the fundamental defect in the brain in fragile X syndrome and, most importantly, found that we can correct this problem in the laboratory," said Warren. "This is quite exciting, progressing from the identification of the gene in 1991 to now believing we will be able to treat a previously untreatable condition." He added that the next steps would be to continue screening and identifying the best drugs likely to correct the deficiencies that result from fragile X syndrome. Fragile X syndrome is caused by a mutation in the FMR1 gene on the X chromosome, the study said. A region of the mutated gene repeats a trinucleotide sequence of DNA bases between 200 and 1,000 times, rather than the normal six to 55 repeats in normal individuals. The abnormal trinucleotide repeats cause the absence of the FMR protein normally produced by the gene, according to the study.
STOCKHOLM Lung cells grown from mouse embryo stem cells have been successfully implanted into the lungs of mice, a breakthrough that could one day help humans with sick lungs. The experiment was conducted by a team of scientists from London's Imperial College and is a "global breakthrough" that "opens up exciting new horizons for the treatment of lung disease," said a report made at th European Respiratory Society's (ERS) annual congress in Stockholm. In the experiment, the researchers injected lung cells cultivated from embryonic stem cells into the mice's lungs. Two days later, they killed the rodents and found that the lung cells had lodged themselves in the animals' lungs, demonstrating the "high degree of specialization of these cells, which attach only to their target organ, that is, the lungs." Embryonic-stem-cell therapy has given rise to hopes for the treatment of many conditions and could one day help repair organs, such as a heart damaged by a heart attack. Experiments suggest stem cells could also yield effective treatments for Parkinson's and Alzheimer's disease, spinal-cord injury, diabetes, osteoarthritis, and numerous other illnesses. But lung diseases have not yet benefited from stem-cell research. One of the great challenges of cell biology is figuring out how stem cells remain unspecialized or "pluripotent," maintaining the capacity to become virtually any type of cell found in blood, nerves, and individual organs. "The lung is a very difficult target for tissue engineering researchers ... especially since it is an extremely complex organ and contains a large variety of cells, some of which have a very slow renewal rate," said researcher Sile Lane of Imperial College. The ERS said the capacity to "regenerate lungs damaged by disease or accident would help tens of millions of patients." But while the study sparked "great hopes," the British researchers noted that human medical applications were "still a long way off."
PARIS A man's testicles could one day provide a plentiful and accessible supply of adult stems cells to help him fight off disease or regenerate damaged organs. Researchers at Weill Cornell Medical College in New York have already isolated the multipurpose cells in mice, and successfully coaxed them to grow into cardiac cells, brain cells, and working blood-vessel tissue. If the same technique can be extended to men, the study points out, it would sidestep the morally charged debate over using embryonic stems cells for the same purpose. In experiments, a team led by Shahin Rafii of the Howard Hughes Medical Institute was able to cultivate "multipotent adult spermatogonial-derived stem cells" (MASCs) without recourse to genetic manipulation. "What is really novel about our work is that ... these mouse stem cells do not require any addition or tweaking of genes to get them to form multi potent cells that then go on to produce all these cell types," said Rafii. The reprogramming of adult cells in connective tissue to produce multipotent stem cells, another technique used, carries an enhanced risk of malignancy, the researchers warned. Spermatogonial progenitor stem cells (SPCs) in the testes are specialized in the generation of the precursor of sperm. "They are remarkably efficient, keeping men fertile well into advanced age," said lead author Marco Seandel, who found a method for growing large quantities of SPCs in the laboratory. Once this step had been mastered, another team set about concocting the perfect biochemical soup for tricking the SPCs to replace their normal function of creating germs cells with their newly assigned task of making "multipotent" stem cells. Stem cells, also found in the embryo and in bone marrow, can grow into almost any kind of cell or tissue in the body. Already used to treat leukemia, they hold enormous promise for the regeneration of failing organs and the treatment of Alzheimer's, Parkinson's, diabetes, arthritis, and a host of other illnesses. One advantage of generating stem cells from the patient is the elimination of any risk of tissue transplant rejection. Extending these techniques to humans-men, in this case-is the next challenge, said Pier Paolo Pandolfi, a professor at Harvard who collaborated in the study published in Nature. The researchers are hoping that the same method of genetic marking that allowed them to isolate the hard-to-spot SPCs in mice will also work for humans. The study speculated that the approach might also work in the female ovary, which also contains a large population of germ cells, but said that experiments to test the theory had yet to be carried out.
PARIS A faulty gene on chromosome 16 boosts the risk of developing type 1 diabetes, according to the latest probe into the causes of this disease. Three variants of a gene called KIAA0350 were spotted as risk factors in a genetic profiling of 563 patients with type 1 diabetes, which were compared with 1,146 healthy people, said the study published by Nature. The research led by Hakon Hakonarson of the Children's Hospital of Philadelphia, Pennsylvania, adds to the list of suspected genes, spotted on chromosomes 6, 11, 1, and 2, each of which appear to play different roles in the disease. Type 1 diabetes is linked to genetic predisposition. The far more common type 2 results mainly from an unhealthy diet and inactivity and is becoming epidemic in scale in many developed or fast-developing countries. Predicting genetic vulnerability to diabetes could offer huge benefits, doctors believe. In most cases of Type 1 diabetes, many patients are diagnosed too late to save the so-called beta cells that produce the insulin. There is no cure for the disease, but earlier warning can encourage dietary change and swifter glucose control, thus helping to stave off potentially life-threatening complications.
WASHINGTON Scientists have identified the genetic blueprint of a parasite that causes disfigurement and debilitating diseases, an advance that could lead to new treatments. The parasite, Brugia malayi, has incapacitated and disfigured more than 40 million people worldwide, according to the World Health Organization. The female worms "can live for up to eight years inside the human body, eventually leading to a ghastly disfiguring disease known as elephantiasis," said the study which appears in Science. People can become infected if bitten by an insect or spider that is carrying the parasite, which can cause a buildup of lymphatic fluid that leads to massive swelling in the head, limbs and trunk of the infected person. "Existing drugs target the larvae and, thus, do not completely kill the worms," said the report. "The drugs often must be taken periodically for years, and the worm can cause a massive immune reaction when it dies and releases foreign molecules in the body." But pinning down the genome of B. malayi will allow scientists to better figure out how to kill it, said lead author Elodie Ghedin of the University of Pittsburgh School of Medicine. "The genomic information gives us a better understanding of what genes are important for different processes in the parasite's life cycle. So, it will now be possible to target these genes more specifically and interrupt its life cycle," said Ghedin. The international team of researchers included several US universities as well as the Imperial College of London, the National Australian University, Canada's Hospital for Sick Children and Germany's University of Gottingen.
PARIS Scientists recently released the finest-detailed map yet of variants in the human genetic code, declaring it should help unlock inherited causes of disease and reveal secrets of evolution. The "second generation" blueprint of human genetic variation, published in the Nature, unveils minute differences in the genome of 270 people, from Nigeria and Utah to China and Japan. Understanding the tiny fraction of material that varies can highlight vulnerability to disease, response to pharmaceutical drugs and reaction to environmental triggers such as ozone pollution and pollen. These variants are usually inherited as small blocks of genetic code, called haplotypes. A first version of the so-called HapMap, published in 2005, uncovered around one million single variants in the genetic code, known as single nucleotide polymorphisms (SNPs, often shorthanded to "Snips"). The higher-resolution update boosts the tally to more than 3.1 million SNPs, according to the compilers, gathered in the International HapMap Consortium. This will boost compare-and-contrast power to investigators seeking to understand why some individuals are prone to a specific ailment while others are immune to it, and why some respond well to a given drug while others react badly. "Researchers around the globe have now associated more than 60 common DNA variants with risk of disease or related traits, with most of the findings coming in the past nine months," said Oxford University, which took part in the project. SNPs, or combinations of them, have already been fingered this year as increasing the risk of coronary artery disease, Crohn's disease, rheumatoid arthritis, and diabetes, it said. In a separate study also published in Nature, scientists at the Broad Institute in Cambridge, Massachusetts, used the new HapMap data to identify two genes in a group of people from Yoruba, Nigeria, that had been shaped by evolutionary pressure. The two genes, called LARGE and DMD, are control cell receptors that are docking points for the Lassa virus. Exposure to this pathogen in Nigera, where the disease is endemic, caused SNP changes in LARGE and DMD that were not seen in samples from populations elsewhere in the world. Similar hallmarks were found in two genes involved in skin pigmentation in people of European ancestry, as were two genes involved in the development of hair follicles in Asians. "Our analysis only scratches the surface of the recent selective history of the human genome," the authors add. M |
