(MEMPHIS, Tenn. \u2013 Month XX, 2026) Sickle cell disease causes premature aging of blood stem cells, which scientists may be able to address with a special class of drugs, according to a new study from St. Jude Children\u2019s Research Hospital. Patients with sickle cell disease experience higher rates of blood stem cell dysfunction and blood cancers compared to their peers, though the reason why has been unclear. The St. Jude researchers found that blood stem cells from young patients with sickle cell disease have features of aging, likely increasing risk for other complications. Giving senolytics, which target aging-related processes, improved disease symptoms in model systems, with implications for curative gene therapies. The findings were published today in Science Translational Medicine.<\/p>\n
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\u201cWe saw that blood stem cells from even young patients with sickle cell disease have many markers of senescence or aging,\u201d said senior co-corresponding author Shannon McKinney-Freeman<\/a>, PhD, St. Jude Department of Hematology<\/a>. \u201cThey become incapable of doing their job of making all other blood cells, including oxygen-carrying red blood cells, but when we gave anti-aging drugs, we eliminated these damaged cells and recovered the lost blood-forming potential in the bone marrow of our models.\u201d<\/p>\n \u00a0<\/p>\n Chronic stress accelerated blood stem cell aging<\/p>\n \u00a0<\/p>\n Sickle cell disease is the most common genetic blood disorder in the world, affecting an estimated 7 million people. In people with the disease, their blood stem cells have a mutation in the gene for hemoglobin, causing the red blood cells they produce to become sickle-shaped and fail to deliver oxygen well. This has many effects, including chronically stressing blood stem cells as they create large amounts of red blood cells to make up for their inefficiency at delivering oxygen to the rest of the body. The researchers sought to understand how that chronic stress impacted these cells, uncovering a massive effect in samples from patients.<\/p>\n \u00a0<\/p>\n \u201cWhen we looked at blood stem cells from children and young patients with sickle cell disease (6-23 years old), we saw their blood stem cells looked much older,\u201d said first author Aditya Barve<\/a>, PhD, St. Jude Department of Hematology. The researchers then implanted the patients\u2019 stem cells in mice and treated them with anti-aging therapy. The treatment significantly decreased markers of senescence, and the scientists saw increased blood formation that matched that of the control group of mice without sickle cell disease that underwent the same process.<\/p>\n \u00a0<\/p>\n To extend the finding, the researchers repeated the process with two Food & Drug Administration (FDA) \u2013approved senolytic drugs, dasatinib and quercetin, given in combination, observing the same positive benefits. Since the drugs are already FDA\u2013approved for another purpose, the approach could move more quickly into clinical testing, including for enhancing ongoing curative gene therapy trials.<\/p>\n \u00a0<\/p>\n Rejuvenating sickle cell disease gene therapy<\/p>\n \u00a0<\/p>\n Recently, potentially curative gene therapy efforts for sickle cell disease have been complicated by variable outcomes. Gene therapy requires a large number of a patient\u2019s blood stem cells, making changes to their DNA to cure or overcome the sickle cell mutation, then transplanting them back into the patient to make normal red blood cells. While gene therapy has the potential to cure a patient, it has experienced setbacks, such as an inability to collect enough viable cells to begin the treatment; in the long term, some patients have developed blood cancers. The aging findings provide senescence as an explanation for the increased disease incidence, and offers an explanation for how to improve both stem cell collection and long-term results.<\/p>\n \u00a0<\/p>\n \u201cWhen we alter cells with gene therapy, we are trying to cure patients for the rest of their lives through what is essentially a bone marrow transplant using their own blood stem cells,\u201d said co-corresponding author Akshay Sharma<\/a>, MBBS, MSc, St. Jude Department of Bone Marrow Transplantation & Cellular Therapy<\/a>. \u201cBefore gene therapy existed, we performed transplants for patients with sickle cell disease using blood stem cells from a donor, trying to find a young and healthy donor, because stem cells that are decades older than the patient may not remain \u2018fit\u2019 for the patient\u2019s lifetime. Our findings show that we also need to consider methods to eliminate the older senescent cells and enrich for young, functional stem cells from a patient before collecting them for gene therapy.\u201d<\/p>\n \u00a0<\/p>\n Current approaches to collecting the many cells needed for gene therapy do not take senescent cells into account. The research provides a provocative jumping point for new research into how doing so, whether through anti-aging senolytics therapy or another mechanism, may improve stem cell collection and the quality of starting material, which may also lead to improvements in gene therapy outcomes.<\/p>\n \u00a0<\/p>\n \u201cBoth anti-aging drugs and gene therapies are still relatively new,\u201d McKinney-Freeman said. \u201cBy combining our knowledge of these new approaches with fundamental research into how sickle cell disease manifests in blood stem cells, we\u2019ve opened a completely new field to explore for improving the lives of the many people impacted by this disorder.\u201d<\/p>\n \u00a0<\/p>\n Authors and funding<\/p>\n The study\u2019s other authors are Preeti Dabas, Adam Cornwell, Pramika Sriram, Alex Kopyov, Emilia Kooienga, Zakiya Kelley, Jacquelyn Myers, Esther Obeng, Guolian Kang, Yunusa Olufadi, Terri Cain, Lindsay Talbot and Dirk Loeffler, St. Jude; James Johnson, WiCell Research Institute; David Spence, University of Tennessee Health Sciences Center; and Mauricio Cortes and Samuel A. Miller, Cellarity Inc.<\/p>\n \u00a0<\/p>\n The study was supported by grants from the National Institute of Health (F32HL164095, R01HL174644, F31HL170678, U01HL163983, R01HL168893, T32CA236748, Leukemia & Lymphoma Society Scholar,<\/p>\n Alex\u2019s Lemonade Stand (Grant # 22-27080), Edward P. Evans Foundation (Discovery Research Grant), American Cancer Society (RSG-22-023-01-CDP) and the American Lebanese Syrian Associated Charities (ALSAC), the fundraising and awareness organization of St. Jude.<\/p>\n \u00a0<\/p>\n St. Jude Media Relations Contact<\/p>\n Michael Sheffield<\/p>\n Desk: (901) 595-0221<\/p>\n Cell: (901) 379-6072<\/p>\n [email\u00a0protected]<\/a> [email\u00a0protected]<\/a><\/p>\n \u00a0<\/p>\n St. Jude\u00a0Children’s Research Hospital<\/p>\n St. Jude\u00a0Children\u2019s Research Hospital is leading the way the world understands, treats, and cures childhood catastrophic diseases. From cancer to life-threatening blood disorders, neurological conditions, and infectious diseases,\u00a0St. Jude\u00a0is dedicated to advancing cures and means of prevention through groundbreaking research and compassionate care. Through global collaborations and innovative science,\u00a0St. Jude\u00a0is working to ensure that every child, everywhere, has the best chance at a healthy future.\u00a0\u00a0To learn more, visit\u00a0stjude.org<\/a>,\u00a0read\u00a0St. Jude\u00a0Progress,\u00a0a digital magazine<\/a>,\u00a0and follow\u00a0St. Jude\u00a0on social media at\u00a0@stjuderesearch<\/a>.<\/p>\n \u00a0<\/p>\n \t\t\t\t\t\t\t\t\t\t