At the Childx conference last week there was a great deal of optimism that stem cell and genetic therapies are about to have a huge impact on many childhood diseases. “It’s not just science fiction anymore,” Matthew Porteus, MD, PhD, told the audience. “We can correct mutations that cause childhood disease.”
The session was hosted by Stanford professor Maria Grazia Roncarolo, MD, who until recently was head of the Italy’s Telethon Institute for Cell and Gene Therapy at the San Raffaele Scientific Institute in Milan. Roncarolo pointed out that there are more than 10,000 human diseases that are caused by a single gene defect. “Stem cell and gene therapies can be used to treat cancer and other diseases,” Roncarolo said.
Two such diseases are sickle cell disease and severe combined immune deficiency. In both cases, a single nucleotide change in DNA becomes a deadly defect for children with the bad luck to have them. Porteus is working on very new genome editing technologies that allow clinicians to go in and fix those DNA typos and cure diseases.
Stanford dermatology researcher Anthony Oro, MD, PhD is working to do something similar with skin cells for a painful blistering disease called epidermolysis bullosa. Children with EB lack a functional gene for one of the proteins that anchors the layers of skin together. Oro and Stanford Institute for Stem Cell Biology and Regenerative Medicine scientist Marius Wernig, MD, PhD, are taking defective skin cells from patients, transforming them into embryonic-like stem cells, fixing the gene defect, and then growing them back into skin stem cells and then layers of skin ready for transplantation. Oro says that they have shown that they can do this in a scalable way in mice, and they hope to start a clinical trial in humans soon.
One of the challenges to genetic therapy is that it often requires putting the gene into blood stem cells to deliver it to the body, but the high dose chemotherapy or radiation that is necessary to remove the bodies own blood stem cells and make way for the transplanted cells is very dangerous in itself. Researchers like Stanford researcher Hiromitsu Nakuchi, MD, PhD, are exploring gentler ways to make space in the body for the transplanted cells. He has discovered that simply by feeding mice a diet deficient in a particular amino acid, blood stem cells begin to die. Other cells in the body don’t seem to be as strongly affected. A dietary solution may eventually allow clinicians to avoid using the highly toxic treatments that have traditionally been used for blood stem cell transplant.
Regenerating and creating new tissues were the theme of separate ChildX talks by Nadia Rosenthal, PhD, of the Australian Regenerative Medicine Institute and Sean Wu, MD, of the Stanford Cardiovascular Institute. Rosenthal looked at the mechanisms that amphibians use in regenerating limbs and explored whether humans might ever be able to make use of similar solutions to help tissues heal instead of scar after injury. Wu looked at organ engineering and wondered if some day we might be able to use biological 3D printers to create a heart or other organs.
Roncarolo’s observation that “the last five years have seen an acceleration of research to bridge the ‘Valley of Death’ between research and application” reflected a general optimism among researchers that stem cell and genetic therapies would soon become reality. But ultimately most of these therapies will have to be scaled up and produced by pharmaceutical companies. Glaxo Smith Kline Senior Vice President Martin Andrews was hopeful too, but pointed out many roadblocks along the way. “In stem cells we are dealing with an inherently variable starting material that can’t be sterilized, and for which the dosages and their timing are all not clear,” Andrews said. “There are a whole range of difficult issues to be overcome.”
Previously: Global health and precision medicine: Highlights from day two of Stanford’s Childx conference, Innovating for kids’ health: More from the first day of Stanford’s Childx, “What we’re really talking about is changing the arc of children’s lives:” Stanford’s Childx kicks off, Countdown to Childx: Global health expert Gary Darmstadt on improving newborn survival, Countdown to Childx: Q&A with pediatric health expert Alan Guttmacher and Countdown to Childx: Stanford expert highlights future of stem cell and gene therapies
Photo of Porteus looking on by Saul Bromberger