{"id":2527,"date":"2015-03-12T00:00:00","date_gmt":"2015-03-12T07:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/immune-system-in-a-dish-offers-hope-for-bubble-boy-disease\/"},"modified":"2015-03-12T00:00:00","modified_gmt":"2015-03-12T07:00:00","slug":"immune-system-in-a-dish-offers-hope-for-bubble-boy-disease","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/de\/news-release\/immune-system-in-a-dish-offers-hope-for-bubble-boy-disease\/","title":{"rendered":"Immune system-in-a-dish offers hope for &#8220;bubble boy&#8221; disease"},"content":{"rendered":"<p>\nLA JOLLA\u2013For infants with severe combined immunodeficiency (SCID), something as simple as a common cold or ear infection can be fatal. Born with an incomplete immune system, kids who have SCID\u2013also known as \u201cbubble boy\u201d or \u201cbubble baby\u201d disease\u2013can\u2019t fight off even the mildest of germs. They often have to live in sterile, isolated environments to avoid infections and, even then, most patients don\u2019t live past a year or two. This happens because stem cells in SCID patients\u2019 bone marrow have a genetic mutation that prevents them from developing critical immune cells, called T and Natural Killer (NK) cells.\n<\/p>\n<p>\nNow, Salk researchers have found a way to, for the first time, convert cells from SCID patients to a stem cell-like state, fix the genetic mutation and prompt the corrected cells to successfully generate NK cells in the laboratory.\n<\/p>\n<p>\n<iframe src=\"\/\/www.youtube.com\/embed\/nlwWIngnCJs\" frameborder=\"0\" allowfullscreen><\/iframe>\n<\/p>\n<p>\nThe success of the new technique suggests the possibility of implanting these tweaked cells back into a patient so they can generate an immune system. Though the new work, published March 12, 2015 in <a href=\"http:\/\/www.cell.com\/cell-stem-cell\/abstract\/S1934-5909(15)00061-2\" target=\"_blank\"><em>Cell Stem Cell<\/em><\/a>, is preliminary, it could offer a potentially less invasive and more effective approach than current options.\n<\/p>\n<p>\n\u201cThis work demonstrates a new method that could lead to a more effective and less invasive treatment for this devastating disease,\u201d says senior author <a href=\"https:\/\/www.salk.edu\/de\/faculty\/verma.html\/\">Inder Verma<\/a>, Salk professor and <a href=\"http:\/\/www.cancer.org\/\" target=\"_blank\">American Cancer Society<\/a> Professor of Molecular Biology. \u201cIt also has the potential to lay the foundation to cure other deadly and rare blood disorders.\u201d\n<\/p>\n<p>\nPrevious attempts to treat SCID involved bone marrow transplants or gene therapy, with mixed results. In what began as promising clinical trials in the 1990s, researchers hijacked virus machinery to go in and deliver the needed genes to newly growing cells in the patient\u2019s bone marrow. While this gene therapy did cure the disease at first, the artificial addition of genes ended up causing leukemia in a few of the patients. Since then, other gene therapy methods have been developed, but these are generally suited for less mild forms of the disease and require bone marrow transplants, a difficult procedure to perform on critically sick infants.<\/p>\n<div class=\"imageCaption\"><img decoding=\"async\" style=\"border-bottom: 1px #006699 solid;\" alt=\"\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/01\/2073-scid-x1.jpg\"><\/p>\n<p>In this new approach to treating &#8220;bubble boy disease,&#8221; a stem cell colony generated from SCID-X1 patient cells (pictured, with cell nuclei in blue), can be genetically corrected and coaxed to grow new immune cells.<\/p>\n<p><a target=\"_blank\" href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/02\/2073-scid-x1.jpg\">Klicken Sie hier<\/a> f\u00fcr ein hochaufl\u00f6sendes Bild.<\/p>\n<p>\nBild: Mit freundlicher Genehmigung des Salk Institute for Biological Studies\n<\/p>\n<\/div>\n<p>\nTo achieve the new method, the Salk team secured a sample of bone marrow from a deceased patient in Australia. Using that small sample, the team developed the new method in three steps. First, they reverted the patient cells into induced pluripotent stem cells (iPSCs)\u2013cells that, like embryonic stem cells, have the ability to turn into any type of tissue and hold vast promise for regenerative medicine.\n<\/p>\n<p>\n\u201cOnce we had patient-derived stem cells, we could remove the genetic mutation, essentially fixing the cells,\u201d explains one of the first authors and Salk postdoctoral researcher Amy Firth.\n<\/p>\n<p>\nThe second innovation was to use new gene editing technology to correct the SCID-related genetic deficiency in these iPSCs. To remove the mutation, the researchers used a technology called TALEN (similar to the better known CRISPR method). This set of enzymes act as molecular scissors on genes, letting researchers snip away at a gene and replace the base pairs that make up DNA with other base pairs.\n<\/p>\n<p>\n\u201cUnlike traditional gene therapy methods, we aren\u2019t putting a whole new gene into a patient, which can cause unwanted side effects,\u201d says Tushar Menon, first author and Salk postdoctoral researcher. \u201cWe use TALEN-based genome editing to change just one nucleotide in one gene to correct the deficiency. The technique is literally that precise.\u201d\n<\/p>\n<p>\nThe third step of the work was to prompt the cells to proliferate into the vital immune system cells\u2013not an easy task, but one that could offer a potentially unlimited supply that can be transplanted back into patients at intervals. To do this, the researchers collaborated with scientists at the University of California, Los Angeles, to use a concoction of nutrients and other factors that would encourage the iPSCs to generate NK cells.\n<\/p>\n<p>\nAnd they succeeded. These corrected cells-in-a-dish did indeed develop mature NK cells.\n<\/p>\n<p>\nNext, the team is working on reproducing the other vital immune components, T cells. So far, they have prompted the iPSCs to turn into the precursors of T cells, but have not yet been able to coax them to maturity.\n<\/p>\n<div class=\"imageCaption530\"><img decoding=\"async\" alt=\"\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/01\/2073.jpg\"><\/p>\n<p>\nFrom left: Tushar Menon, Inder Verma and Amy Firth<\/p>\n<p><a target=\"_blank\" href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/02\/2073.jpg\">Klicken Sie hier<\/a> f\u00fcr ein hochaufl\u00f6sendes Bild.<\/p>\n<p>\nBild: Mit freundlicher Genehmigung des Salk Institute for Biological Studies\n<\/p>\n<\/div>\n<p>\n\u201cUltimately, we hope these efforts will help lead to the \u2018holy grail\u2019 in the field: the ability to create stem cells from iPSCs capable of generating all types of blood and immune cells,\u201d says Verma, who is also the Irwin and Joan Jacobs Chair in Exemplary Life Science. The ability to generate the corrected blood stem cells themselves could yield a one-time treatment that would ultimately replenish functioning cells throughout a patient\u2019s whole life.\n<\/p>\n<p>\n\u201cIn lieu of that happening, we have an alternative that could work as a less invasive treatment and with the ability to easily scale up to mass quantities,\u201d says Firth. Another benefit to using patient-derived cells as treatment is that the patient\u2019s body typically won\u2019t reject them (unlike donor tissue).\n<\/p>\n<p>\nOther authors on the paper include: Susan Qualls, William Gilmore,<br \/>\nEugene Ke, Oded Singer, Leif Anderson and Alexander Bornzin from the Salk Institute; Deirdre Scripture-Adams, Zoran Galic and Jerome Zack from <a href=\"http:\/\/www.ucla.edu\/\" target=\"_blank\">UCLA<\/a>; and Ian Alexander of the <a href=\"http:\/\/www.cmri.org.au\/\" target=\"_blank\">Children\u2019s Medical Research Institute<\/a> und <a href=\"http:\/\/www.schn.health.nsw.gov.au\/\">The Children\u2019s Hospital at Westmead<\/a> in Australia.\n<\/p>\n<p>\nThis work was supported in part by grants from Ipsen\/Biomeasure, Sanofi Aventis, the <a href=\"http:\/\/www.hnberger.org\/\" target=\"_blank\">H.N. and Frances C. Berger Foundation<\/a>, der <a href=\"http:\/\/helmsleytrust.org\/\" target=\"_blank\">Die gemeinn\u00fctzige Stiftung von Leona M. und Harry B. Helmsley<\/a> und die <a href=\"https:\/\/www.cirm.ca.gov\/\" target=\"_blank\">California Institute for Regenerative Medicine<\/a>.\n<\/p>\n<p>\n<strong>\u00dcber das Salk Institute for Biological Studies:<\/strong><br \/>\nThe Salk Institute for Biological Studies is one of the world&#8217;s preeminent basic research institutions, where internationally renowned faculty probes fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer&#8217;s, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.\n<\/p>\n<p>\nFaculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, MD, the Institute is an independent nonprofit organization and architectural landmark.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[115],"disease-research":[122],"class_list":["post-2527","disclosure","type-disclosure","status-publish","hentry","faculty-inder-verma","disease-research-immune-system-biology"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Immune system-in-a-dish offers hope for &quot;bubble boy&quot; disease - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/de\/news-release\/immune-system-in-a-dish-offers-hope-for-bubble-boy-disease\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Immune system-in-a-dish offers hope for &quot;bubble boy&quot; disease - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2013For infants with severe combined immunodeficiency (SCID), something as simple as a common cold or ear infection can be fatal. 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