Scientists create personalized stem cells for patients with ALS

        The Los Angeles Times (8/1, Kaplan) reports that researchers from Harvard University and Columbia University "have created the first personalized stem cells for patients with" amyotrophic lateral sclerosis (ALS), more commonly known as Lou Gehrig’s disease, "by rewinding their skin cells to an embryonic state, according to a study published Thursday in the online edition of Science." During previous experiments, "human versions of the so-called induced pluripotent stem (iPS) cells had only been made from skin samples provided by healthy subjects."

        But the Harvard-Columbia team used "skin cells from two" sisters, aged 82 and 89, who both had ALS, added the AP (7/31, Schmid). The researchers "were able to reprogram the cells into a type of adult stem cell, and from that into nerve cells." Co-author Chris Henderson, M.D., co-director of the Center for Motor Neuron Biology and Disease at Columbia University, said, "What we now have in the culture dish is cells that have the same genetic makeup as the ALS patient, and they are the same cells that are affected by the disease." This "means that, for the first time, scientists hope to be able to observe the development of the disease in the cells and, from that, possibly begin studies of treatments." Dr. Henderson added, "There is no way we could go to an ALS patient and take these cells."

        The "neural cells were derived by the team using a method first developed by Shinya Yamanaka, a researcher at Kyoto University in Japan," reports Bloomberg (8/1, Waters). The process "involves inserting four different genes into the skin cells, causing them to revert to a primordial state similar to embryonic stem cells." Bloomberg points out that the "immediate potential of the method is that it will reveal the chemical and molecular changes that occur in motor neurons before they degenerate." Furthermore, it will enable scientists "to test libraries of chemical compounds on the cells to see if they can intervene in this process." The method, however, "uses viruses to ferry the genes into the cells," which "can trigger cancer and other undesired effects." Notably, teams throughout the globe "are now looking for alternative methods of reprogramming cells without using viruses."

        Nevertheless, the Harvard-Columbia team can claim "success at what researchers have long been racing to do: create in the laboratory a plentiful supply of cells that have the same genetic makeup as a patient with a particular disease," notes the Boston Globe (8/1, Johnson). The group "had planned to create genetically matched stem cells through cloning patients’ cells, a process that not only involves some medical risk to women who serve as egg donors, but also requires the destruction of embryos."

        Instead, Harvard researcher Kevin Eggan, and colleagues, modified "skin fibroblasts from [the] 82-year-old patient with familial ALS…to express four oncogenes, including KLF4, SOX2, OCT4, and c-MYC," reported MedPage Today (7/31, Gever). Next, "[a]fter the oncogene-retroviral transformation, the researchers chose colonies that developed from the 82-year-old’s cells for the rest of their studies." The team isolated "pluripotent stem cells," and "treated them with retinoic acid and an agent that stimulates the so-called sonic hedgehog cell-differentiation pathway." The investigators discovered that the "resulting cells carried numerous markers of natural human motor neurons." Notably, both women "carried a mutation in the superoxide dismutase gene that causes a hereditary, slowly-progressing form of ALS."

        And, "experiments with cells from mice carrying SOD1 mutations suggest that support cells called astrocytes release a toxic factor that kills the motor neurons," according to New Scientist (7/31, Aldhous). Therefore, the researchers "may have to also grow astrocytes, but" they are "confident that they can be created from iPS cells." In addition, they will "also need to show that the cells they have created can function as motor neurons." Eggan said that "the cells’ function will [eventually] be tested by transplanting them into the spinal cords of chick and mouse embryos." Time (7/31, Park), NPR‘s (7/31, Palca) All Things Considered, the U.K.’s Press Association (8/1), the U.K.’s Guardian (7/31, Sample), the U.K.’s Telegraph (7/31, Highfield), the U.K.’s Independent (8/1, Connor), and HealthDay (7/31, Gardner) also covered the story.