Genetic base editing treats sickle cell disease in mice

(Broad Institute of MIT and Harvard) Sickle cell disease leads to chronic pain, organ failure, and early death in patients worldwide. A team led by Broad Institute of MIT and Harvard and St. Jude Children's Research Hospital has demonstrated a gene editing approach that efficiently corrects the mutation underlying SCD in patient blood stem cells and in mice. This treatment rescued disease symptoms in animal models, enabling long-lasting production of healthy blood cells, and could inspire a therapeutic strategy for SCD.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news

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Abstract Sickle cell disease (SCD) is a highly complex inherited disorder of hemoglobin structure. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of the disease. Its manifestations could be acute, chronic, nociceptive, neuropathic that could occur singly or in various combinations. Pain continues to be the major factor of SCD phenotypic complications and the most common cause of admissions to the Emergency Department and/or the hospital. Although progress has been made in understand...
Source: Complementary Therapies in Medicine - Category: Complementary Medicine Authors: Tags: Complement Ther Med Source Type: research
Abstract Sickle cell disease afflicts millions of people worldwide and approximately 100,000 Americans. Complications are myriad and arise as a result of complex pathological pathways 'downstream' to a point mutation in DNA, and include red blood cell membrane damage, inflammation, chronic hemolytic anemia with episodic vaso-occlusion, ischemia and pain, and ultimately risk of cumulative organ damage with reduced patient lifespan. The National Heart, Lung, and Blood Institute's 2014 evidence-based guideline for sickle cell disease -management states additional research is needed before investigational curative the...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
In this study, we reviewed the outcome of SCD patients who underwent transplant at our institution using standard protocols (NMA regimen in patients ≥14 years and myeloablative regimen in
Source: Blood - Category: Hematology Authors: Tags: 732. Clinical Allogeneic Transplantation: Results: Poster II Source Type: research
Conclusions: Early results from 2 SCA adults treated with a modified -globin LV modified autologous HSC following RIC transplant showed excellent safety, feasibility, with minimal post-transplant toxicity, rapid count recovery, and sustained stable genetically modified cells in peripheral blood and bone marrow. The first patient shows significant clinical amelioration of the SCA phenotype at 1 year PT, with 20% vector-derived HbF (HbF*) that has caused amelioration of anemia, near elimination of chronic pain and absence of acute sickle events. The second patient, although still early post-transplant shows a similar HbF* tr...
Source: Blood - Category: Hematology Authors: Tags: 801. Gene Therapy and Transfer: Gene Therapy for Blood Cell Disorders Source Type: research
Conclusions: We established the microglia-like nature of the cultured PBMCs derived from patients with SCD±CP and normal blood donors through morphologic examination and confirmation of characteristic surface markers via flow and fluorescence microscopy, and through demonstration of activation with LPS. Our microglial-like cells derived from patients with SCD CP+ were activated at higher percentages by LPs treatment than microglial-like cells derived from normal human blood donors and SCD CP-, suggesting that donor characteristics are retained by the microglial-like cells developed in culture. We propose to use this...
Source: Blood - Category: Hematology Authors: Tags: 113. Hemoglobinopathies, Excluding Thalassemia-Basic and Translational Science: Poster I Source Type: research
Pain is one of the most dreadful symptoms in sickle cell disease (SCD) and is often refractory to currently available analgesics. Besides acute painful vaso-occlusive crises, SCD is also accompanied by intractable chronic pain. This persistent, and often unrelieved, pain starts early in childhood and continues throughout life. The neurobiological mechanisms of chronic pain in SCD remain unclear, which markedly limits effective pain management and the quality of life in patients with SCD. Taking advantage of two humanized mouse models of SCD, this study aimed to investigate protein phosphorylation mechanisms for chronic pai...
Source: Blood - Category: Hematology Authors: Tags: 113. Hemoglobinopathies, Excluding Thalassemia-Basic and Translational Science: Poster III Source Type: research
Background: Sickle Cell Disease (SCD) is a devastating inherited disease, characterized by polymerization of sickle hemoglobin under deoxygenated conditions that can lead to acute pain crises, ischemia, and chronic organ damage. Pharmacologic anti-sickling agents that decrease polymerization are currently under investigation, however there is no consistent in vitro system to study these compounds; whole patient blood, subject to clinical variability and limited supply, is most often used. Human Umbilical Cord Derived Erythroid Progenitor 2 cells (HUDEP2) are an immortalized CD34+ hematopoietic stem cell (HSC) derived eryth...
Source: Blood - Category: Hematology Authors: Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Poster III Source Type: research
Sickle cell anemia is a form of anemia in which there aren’t enough healthy red blood cells to carry enough oxygen throughout your body. General symptoms include fatigue and joint pain with periods of intense pain that can last either hours or weeks. Revee Agyepong, a 17-year-old from Edmonton, Canada, suffered from sickle cell anemia with symptoms of chronic bone and joint pain, irregular heartbeat, kidney stones and shortness of breath. “I thought that everyone would go out for recess and play, then come back with a terrible headache and body pain, couldn’t breathe … eventually I&n...
Source: Cord Blood News - Category: Perinatology & Neonatology Authors: Tags: blood disorder Cord Blood medical research stem cells Source Type: blogs
Sickle cell disease (SCD) is 1 of the most common genetic diseases that affects millions of individuals worldwide. The severity of symptoms cannot be predicted based solely on the genotype. However, in most patients it is associated with early mortality and unfavorable impact on quality of life [1], with recurrent episodes of pain accompanied by progressive damage to vital organs, such as lung, brain, spleen, and kidney [2,3]. Advances in supportive care, including usage of hydroxyurea, have led to improvements in early survival, creating a growing proportion of young adults with chronic health issues related to SCD [4,5].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Summary Recurrent chronic leg ulcers are among the most severe vasculopathic complications of sickle cell disease (SCD). Their treatment remains a challenge. Stem cell therapy with bone marrow mononuclear cells (BMMC) is a promising new therapeutic option for other forms of chronic ulcers. This prospective pilot study was performed to evaluate safety and feasibility of BMMC implantation in patients with SCD and chronic leg ulcers (SCLU). Ulcer closure, recurrence and local pain were evaluated. BMMC were successfully administered to 23 SCLU patients and no serious adverse events occurred. During the 6‐month follow‐up pe...
Source: British Journal of Haematology - Category: Hematology Authors: Tags: Research Paper Source Type: research
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