Syndicate content

Archive - Apr 5, 2012

Stem Cell Work Permits Production of Unlimited Quantities of Cystic Fibrosis Lung Tissue for Drug Testing

Harvard stem cell researchers at Massachusetts General Hospital (MGH) have taken a critical step in perhaps making possible the discovery, in the relatively near future, of a drug to control cystic fibrosis (CF), a fatal lung disease that claims about 500 lives each year, with 1,000 new cases diagnosed annually. Beginning with the skin cells of patients with CF, Jayaraj Rajagopal, M.D., and colleagues first created induced pluripotent stem (iPS) cells, and then used those cells to create human disease-specific functioning lung epithelium, the tissue that lines the airways and is the site of the most lethal aspect of CF, where the mutant genes cause irreversible lung disease and inexorable respiratory failure. That tissue, which researchers can now grow in unlimited quantities in the laboratory, contains the delta-508 mutation, the mutation responsible for about 70 percent of all CF cases and 90 percent of the ones in the United States. The tissue also contains the G551D mutation, a mutation that is involved in about 2 percent of CF cases and the one cause of the disease for which there is now a drug. The work is featured on the cover of the April 6, 2012 issue of Cell Stem Cell. Postdoctoral fellow Hongmei Mou, Ph.D., is first author on the paper, and Dr. Rajagopal is the senior author. Dr. Mou credits learning the underlying developmental biology in mice as the key to making tremendous progress in only two years. "I was able to apply these lessons to the iPS cell systems," she said. "I was pleasantly surprised the research went so fast, and it makes me excited to think important things are within reach.

Spontaneous Mutations Linked to Autism Risk with Older Dads

Researchers have turned up a new clue to the workings of a possible environmental factor in autism spectrum disorders (ASDs): fathers were four times more likely than mothers to transmit tiny, spontaneous mutations to their children with the disorders. Moreover, the number of such transmitted genetic changes increased with paternal age. The discovery may help to explain earlier evidence linking autism risk to older fathers. The results are among several from a trio of new studies, supported in part by the National Institutes of Health, finding that such sequence changes in parts of genes that code for proteins play a significant role in ASDs. One of the studies determined that having such mutations boosts a child's risk of developing autism 5 to 20 fold. Taken together, the three studies represent the largest effort of its kind, drawing upon samples from 549 families to maximize statistical power. The results reveal sporadic mutations widely distributed across the genome, sometimes conferring risk and sometimes not. While the changes identified don't account for most cases of illness, they are providing clues to the biology of what are likely multiple syndromes along the autism spectrum. "These results confirm that it's not necessarily the size of a genetic anomaly that confers risk, but its location – specifically in biochemical pathways involved in brain development and neural connections. Ultimately, it's this kind of knowledge that will yield potential targets for new treatments," explained Thomas R. Insel, M.D., director of the NIH's National Institute of Mental Health (NIMH), which funded one of the studies and fostered development of the Autism Sequencing Consortium, of which all three groups are members.