Dr. Ewelina Mamcarz and Dr. Stephen Gottschalk. Photo by Smithsonian Magazine.
A treatment that has successfully generated immune systems in several patients born with X-linked severe combined immune deficiency has been honored with a Smithsonian magazine American Ingenuity Award for Life Sciences.
The therapy uses the bone marrow of the patients and a lentivirus that “installs” a copy of the gene to activate the immune system in the cells. The therapy was developed by Brian Sorrentino, M.D., a St. Jude Children’s Research Hospital faculty member who died in late 2018.
Sorrentino and St. Jude faculty members Ewelina Mamcarz, M.D., and Stephen Gottschalk, M.D., join other American Ingenuity Award 2019 recipients Lil Nas X, Jose Andres, Amy Sherald, Alex Kipman, Sheperd Doeleman and the Event Horizon Telescope Team and Heidi Schreck. The eighth annual American Ingenuity Awards honor individuals across seven wide-ranging categories: Youth, Visual Arts, Social Progress, Technology, Life Sciences, Physical Sciences and Performing Arts. The winners will be featured in Smithsonian magazine’s special December American Ingenuity Awards issue, which is available at smithsonianmag.com/ingenuity, and will be on newsstands Nov. 26.
“The American Ingenuity Awards honor individuals who are spearheading revolutionary change in society,” said Maria Keehan, creative director of Smithsonian magazine. “We are celebrating visionaries across a multitude of platforms, from those aiding disaster victims worldwide to those developing a life-saving gene therapy or redefining what it means to mix genres in music. We are proud to honor this year’s class, all of whom are at the top of their respective fields.”
Infants born with XSCID, also known as “bubble boy disease,” have a mutated interleukin-2 receptor subunit gamma (IL2RG) that doesn’t allow them to produce functional immune cells. Without functional immune cells, these infants are extremely susceptible to any type of infection. Untreated, the children usually die early in life.
Results from a trial using the gene therapy to treat patients at St. Jude Children’s Research Hospital appeared in the New England Journal of Medicine in April. At publication time, eight infants had been successfully treated with the therapy. They have since been discharged from the hospital and are living with their families. Since the paper’s publication, two more infants have been treated.
“Some of these patients are toddlers now, are responding to vaccinations and have immune systems they need for protection from infections as they explore the world and live normal lives,” said Mamcarz, who was first and corresponding author on the New England Journal of Medicine paper.
The gene therapy is modeled on the human immunodeficiency virus that has been re-engineered to carry a normal copy of the IL2RG gene into blood stem cells taken from the patients. The viral vector includes insulators to block the activation of genes that could cause patients to develop leukemia, which was the result in previous attempts to use a viral vector to treat XSCID patients.
“It is a great honor to receive the Smithsonian magazine’s Ingenuity Award for the St. Jude XSCID gene therapy program,” said Gottschalk, chair of the hospital's Department of Bone Marrow Transplantation and Cellular Therapy. Gottschalk and Mamcarz are principal investigators on the clinical trial, which was conducted in close collaboration with investigators at the University of California, San Francisco, Mort Cowan, M.D., and Jennifer Puck, M.D.; and at the National Institute of Allergy and Infectious Diseases, Harry Malech, M.D., and Suk See De Ravin, M.D., PhD.
Past winners include Elon Musk, SpaceX and Tesla founder; Jeff Bezos, Amazon founder; Janelle Monae, singer-songwriter; John Legend, Grammy-winning musician; John Krasinski, writer and actor; Tracy K. Smith, United States, Poet Laureate; Dave Eggers, novelist; Jony Ive, Apple designer; Lin-Manuel Miranda, writer and composer of Hamilton; and the Parkland survivors who created the March for Our Lives.
“Since its founding, St. Jude has accomplished many milestones to advance cures for pediatric catastrophic diseases,” said James R. Downing, M.D., St. Jude president and chief executive officer. “For years, the late Brian Sorrentino and his team dedicated their work to finding a cure for the immune disorder. Their achievement shows the power of persistence and what can be accomplished when determined individuals work together to achieve a better tomorrow for children in need.”
Other authors on the New England Journal of Medicine paper are: Sheng Zhou, Timothy Lockey, Hossam Abdelsamed, Shane Cross, Guolian Kang, Zhijun Ma, Jose Condori, Jola Dowdy, Brandon Triplett, Chen Li, Gabriela Maron, Xing Tang, William Janssen, Byoung Ryu, Mitchell Weiss, Benjamin Youngblood and Michael Meagher, all of St. Jude; Juan Carlos Aldave Becerra, Hospital Nacional Edgardo Rebagliati Martins, Peru; Joseph Church, Children’s Hospital Los Angeles; Elif Dokmeci, University of New Mexico; James Love, University of Oklahoma Health Sciences Center, Tulsa; Ana Carolina da Matta Ain, University of Taubaté, Brazil; Hedi van der Watt, Copperfield Childcare, Claremont, South Africa; Janel Long-Boyle, University of California, San Francisco.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 50 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food — because all a family should worry about is helping their child live. To learn more, visit stjude.org or follow St. Jude on social media at @stjuderesearch.