A5018029184- Virus-based gene therapy research
- CAR-T cell therapy research
- Lysosomal Storage Disorders Research
- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Trypanosoma species research and implications
- Immunotherapy and Immune Responses
- Carbohydrate Chemistry and Synthesis
- Hemophilia Treatment and Research
- T-cell and B-cell Immunology
- Biochemical and Molecular Research
- Platelet Disorders and Treatments
- Immunodeficiency and Autoimmune Disorders
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Child Nutrition and Feeding Issues
- Adenosine and Purinergic Signaling
- RNA regulation and disease
- Cell Adhesion Molecules Research
- Chronic Myeloid Leukemia Treatments
- Effects of Radiation Exposure
- Glycosylation and Glycoproteins Research
Swedish Orphan Biovitrum (Sweden)
2024
Svenska Örtmedicinska Institute
2017
Karolinska Institutet
2014-2016
University of Florida
2006-2015
Florida College
2013
Cancer cells exhibit altered glucose metabolism characterized by a preference for aerobic glycolysis or the Warburg effect, and resist matrix detachment-induced apoptosis, which is called anoikis, barrier to metastasis. It remains largely unclear whether tumor influences anoikis Here we show that when detached from matrix, untransformed mammary epithelial undergo metabolic reprogramming markedly upregulating pyruvate dehydrogenase (PDH) kinase 4 (PDK4) through estrogen-related receptor gamma...
Normal cells require adhesion to extracellular matrix for survival. Cell detachment causes a drastic increase in reactive oxygen species (ROS) that promotes anoikis. In the present study, we observed upon from matrix, human mammary epithelial strongly upregulate manganese superoxide dismutase (MnSOD, or SOD2), principal mitochondrial antioxidant enzyme detoxifies ROS through dismutation of superoxide. Induction MnSOD by cell is dependent on NFκB transcription factor. Detachment potently...
Gene therapy strategies for congenital myopathies may require repeat administration of adeno-associated viral (AAV) vectors in response to several limitations inherent the clinical design: 1) doses below therapeutic efficacy patients enrolled early phase trials; 2) progressive reduction gene expression over time as a result increasing muscle mass treated at young age; and 3) possibly faster depletion pathogenic myofibers this patient population. Immune responses triggered by first vector...
Naturally occurring regulatory T cells (Treg) express high levels of glucocorticoid-induced tumour necrosis factor receptor (GITR). However, studies the role GITR in Treg biology has been complicated by observation that upon activation effector CD4+ (Teff) also receptor. Here, we dissect contribution GITR-induced signaling networks expansion and function FoxP3+ Treg. We demonstrate a high-affinity soluble Fc-GITR-L dimer, conjugation with αCD3, specifically enhances vitro proliferation Treg,...
Pompe disease is an autosomal recessive disorder caused by mutations in the acid-α glucosidase (GAA) gene. Lingual dysfunction prominent but does not respond to conventional enzyme replacement therapy (ERT). Using (Gaa−/−) mice, we tested hypothesis that intralingual delivery of viral vectors encoding GAA results expression and glycogen clearance both tongue myofibers hypoglossal (XII) motoneurons. An injection adeno-associated virus (AAV) vector (serotypes 1 or 9; × 1011 genomes, CMV...
Immune responses to factor IX (F.IX), a major concern in gene therapy for hemophilia, were analyzed adeno-associated viral (AAV-2) transfer skeletal muscle and liver as function of the F9 underlying mutation. Vectors identical those recently used clinical trials administered four lines hemophilia B mice on defined genetic background [C3H/HeJ with deletion endogenous transgenic range nonfunctional human F.IX (hF.IX) variants]. The strength immune response AAV-encoded inversely correlated...
Gene therapy for hemophilia B has been shown to result in long-term expression and immune tolerance factor IX (F.IX) after vivo transduction of hepatocytes with adeno-associated viral (AAV-2) vectors experimental animals. An optimized protocol was effective several strains mice a 9 gene deletion (F9(-/-)). However, responses against F.IX were repeatedly observed C3H/HeJ F9(-/-) mice. We sought establish transfer that results sustained without requirement additional manipulation the system....
Gene and protein replacement therapies for inherited deficiencies such as hemophilia or lysosomal storage disorders are limited by deleterious immune responses directed against their respective therapeutic proteins. Therefore, the development of protocols preventing is key to providing successful long-term therapy.
Pompe disease is a progressive neuromuscular disorder caused by lysosomal accumulation of glycogen from deficiency in acid alpha-glucosidase (GAA). Replacement the missing enzyme available repeated protein infusions; however, efficacy limited immune response and inability to restore enzymatic function central nervous system. An alternative therapeutic option adeno-associated virus (AAV)-mediated gene therapy, which results widespread transfer prolonged transgene expression. Both replacement...
Background Hepatic gene transfer, in particular using adeno-associated viral (AAV) vectors, has been shown to induce immune tolerance several protein antigens. This approach exploited animal models of inherited deficiency for systemic delivery therapeutic proteins. Adequate levels transgene expression hepatocytes a suppressive T cell response, thereby promoting tolerance. study addresses the question whether AAV transfer can cytoplasmic protein. Major Findings AAV-2 vector-mediated hepatic...
Intramuscular (IM) administration of an adeno-associated viral (AAV) vector represents a simple and safe method gene transfer for treatment the X-linked bleeding disorder hemophilia B (factor IX, F.IX, deficiency). However, approach is hampered by increased risk immune responses against F.IX. Previously, we demonstrated that drug cocktail suppressants rapamycin, IL-10, specific peptide (encoding dominant CD4(+) T cell epitope) caused induction regulatory cells (Treg) with concomitant...
Enzyme replacement therapy (ERT) with recombinant human acid-α-glucosidase (rhGAA) is the only FDA approved for Pompe disease. Without ERT, severely affected individuals (early onset) succumb to disease within 2 years of life. A spectrum severity and progression exists depending upon type mutation in GAA gene (GAA), which turn determines amount defective protein produced its enzymatic activity. large percent early onset patients are also cross reactive immunological material negative (CRIM-)...
Background: Immune tolerance induction (ITI) is the gold standard for inhibitor eradication to restore clinical efficacy of factor replacement therapy in haemophilia. However, as ITI often requires frequent administration over extended periods, it can be considered burdensome patients and healthcare resources. Therefore, there a need optimise treatment, particularly who failed previous attempts. Objectives: The ReITIrate study aimed prospectively evaluate rescue with efmoroctocog alfa, an...