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OTL-103
OTL-103 (GSK-2696275) is a gene therapy for Wiskott–Aldrich syndrome, a rare primary immunodeficiency caused by mutations in the gene that codes for Wiskott–Aldrich syndrome protein (WASp). It was developed by Orchard Therapeutics in conjunction with GlaxoSmithKline. It is currently undergoing Phase I/II of clinical trials that are expected to conclude in October 2025. Development history OTL-103 is based on the lentiviral vector technology licensed from GlaxoSmithKline by Orchard Therapeutics in 2020. In 2019, the Food and Drug Administration granted OTL-103 Regenerative Medicine Advanced Therapy status. In the same year, the first clinical trial using OTL-103 for severe cases of Wiskott–Aldrich syndrome began at the San Raffaele Hospital in Milan, Italy. Orchard Therapeutics expected to file a Biologics License Application with the Food and Drug Administration in 2021, however, due to the COVID-19 pandemic's impact on drug development, this was postponed to 2022. Mecha ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Wiskott–Aldrich Syndrome Protein
The Wiskott–Aldrich Syndrome protein (WASp) is a 502-amino acid protein expressed in cells of the hematopoietic system that in humans is encoded by the ''WAS'' gene. In the inactive state, WASp exists in an autoinhibited conformation with sequences near its C-terminus binding to a region near its N-terminus. Its activation is dependent upon CDC42 and PIP2 acting to disrupt this interaction, causing the WASp protein to 'open'. This exposes a domain near the WASp C-terminus that binds to and activates the Arp2/3 complex. Activated Arp2/3 nucleates new F-actin. WASp is the founding member of a gene family which also includes the broadly expressed N-WASP (neuronal Wiskott–Aldrich Syndrome protein), SCAR/ WAVE1, WASH, WHAMM, and JMY. WAML (WASP and MIM like), WAWH (WASP without WH1 domain), and WHIMP (WAVE Homology in Membrane Protrusions) have more recently been discovered. Structure and function The Wiskott–Aldrich syndrome (WAS) family of proteins share similar dom ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Regenerative Medicine Advanced Therapy
Regenerative Medicine Advanced Therapy (RMAT) is a designation given by the Food and Drug Administration to drug candidates intended to treat serious or life-threatening conditions under the 21st Century Cures Act. A RMAT designation allows for accelerated approval based surrogate or intermediate endpoints. RMAT goes beyond breakthrough therapy features by allowing for accelerated approval of drugs based on surrogate endpoints. A surrogate endpoint is a biomarker that substitutes for a direct endpoint, such as clinical benefit. Legal background Section 3033 of the 21st Century Cures Act introduces section 506(g) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) that allows for the designation of certain therapies as a 'regenerative medicine advanced therapy' (RMAT) (). Qualifying criteria In order to qualify for RMAT status, a treatment must # meet the definition of a regenerative medicine therapy, # intend to treat, modify, reverse or cure a serious condition, and # ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Wiskott–Aldrich Syndrome
Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia (low platelet count), immune deficiency, and bloody diarrhea (secondary to the thrombocytopenia). It is also sometimes called the eczema-thrombocytopenia-immunodeficiency syndrome in keeping with Aldrich's original description in 1954. The WAS-related disorders of X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN) may present with similar but less severe symptoms and are caused by mutations of the same gene. Signs and symptoms WAS occurs most often in males due to its X-linked recessive pattern of inheritance, affecting between 1 and 10 males per million. The first signs are usually petechiae and bruising, resulting from a low platelet count (i.e. thrombocytopenia). Spontaneous nose bleeds and bloody diarrhea are also common and eczema typically develops within the first month of life. Recurrent bacterial infections typically develop by three month ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD34
CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first described on hematopoietic stem cells independently by Civin et al. and Tindle et al. as a cell surface glycoprotein and functions as a cell-cell adhesion factor. It may also mediate the attachment of hematopoietic stem cells to bone marrow extracellular matrix or directly to stromal cells. Clinically, it is associated with the selection and enrichment of hematopoietic stem cells for bone marrow transplants. Due to these historical and clinical associations, CD34 expression is almost ubiquitously related to hematopoietic cells; however, it is actually found on many other cell types as well. Function The CD34 protein is a member of a family of single-pass transmembrane sialomucin proteins that show expression on early haematopoietic and vascul ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Experimental Drugs
An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs when a particular factor is manipulated. Experiments vary greatly in goal and scale but always rely on repeatable procedure and logical analysis of the results. There also exist natural experimental studies. A child may carry out basic experiments to understand how things fall to the ground, while teams of scientists may take years of systematic investigation to advance their understanding of a phenomenon. Experiments and other types of hands-on activities are very important to student learning in the science classroom. Experiments can raise test scores and help a student become more engaged and interested in the material they are learning, especially when used over time. Experiments can vary from personal and informal natural comparisons (e. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gene Therapy
Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DNA was performed in 1980, by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989. The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990. It is thought to be able to cure many genetic disorders or treat them over time. Between 1989 and December 2018, over 2,900 clinical trials were conducted, with more than half of them in phase I.Gene Therapy Cli ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Infusion Therapy
In medicine, infusion therapy deals with all aspects of fluid and medication infusion, via intravenous or subcutaneous application. A special infusion pump can be used for this purpose. A fenestrated catheter is most frequently inserted into the localized area to be treated. There are a range of delivery methods for infusion of drugs via catheter: *Electronic Pump: Drugs are often pre-mixed from vials and stored in infusion bags to be delivered by electronic pump. *Elastomeric pump *Pre-Filled Infusion Therapy: with this latest technology, a unit dose can be metered to the location from a pre-filled container. Infusion therapy has a range of medical applications including sedation, anesthesia, post-operative analgesic pain management, chemotherapy, and treatment of infectious diseases Advantages of infusion therapy over other non-site-specific delivery methodologies are primarily efficacy through precision of medication delivery. New standards for infusible pharmaceuticals have b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lentiviral Vector In Gene Therapy
Lentiviral vectors in gene therapy is a method by which genes can be inserted, modified, or deleted in organisms using lentiviruses. Lentiviruses are a family of viruses that are responsible for diseases like AIDS, which infect by inserting DNA into their host cells' genome. Many such viruses have been the basis of research using viruses in gene therapy, but the lentivirus is unique in its ability to infect non-dividing cells, and therefore has a wider range of potential applications. Lentiviruses can become endogenous (ERV), integrating their genome into the host germline genome, so that the virus is henceforth inherited by the host's descendants. To be effective in gene therapy, there must be insertion, alteration and/or removal of host cell genes. To do this, scientists use the lentivirus' mechanisms of infection to achieve a desired outcome to gene therapy. To understand the capabilities of a lentiviral vector, one has to consider the biology of the infection process. The l ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Transfection
Transfection is the process of deliberately introducing naked or purified nucleic acids into eukaryotic cells. It may also refer to other methods and cell types, although other terms are often preferred: "transformation" is typically used to describe non-viral DNA transfer in bacteria and non-animal eukaryotic cells, including plant cells. In animal cells, transfection is the preferred term as transformation is also used to refer to progression to a cancerous state (carcinogenesis) in these cells. Transduction is often used to describe virus-mediated gene transfer into eukaryotic cells. The word ''transfection'' is a portmanteau of ''trans-'' and ''infection''. Genetic material (such as supercoiled plasmid DNA or siRNA constructs), may be transfected. Transfection of animal cells typically involves opening transient pores or "holes" in the cell membrane to allow the uptake of material. Transfection can be carried out using calcium phosphate (i.e. tricalcium phosphate), by ele ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Peripheral Blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the circulatory system is also known as ''peripheral blood'', and the blood cells it carries, ''peripheral blood cells''. Blood is composed of blood cells suspended in blood plasma. Plasma, which constitutes 55% of blood fluid, is mostly water (92% by volume), and contains proteins, glucose, mineral ions, hormones, carbon dioxide (plasma being the main medium for excretory product transportation), and blood cells themselves. Albumin is the main protein in plasma, and it functions to regulate the colloidal osmotic pressure of blood. The blood cells are mainly red blood cells (also called RBCs or erythrocytes), white blood cells (also called WBCs or leukocytes) and platelets (also called thrombocytes). The most abundant cells in vertebrate blo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bone Marrow
Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic cells, marrow adipose tissue, and supportive stromal cells. In adult humans, bone marrow is primarily located in the ribs, vertebrae, sternum, and bones of the pelvis. Bone marrow comprises approximately 5% of total body mass in healthy adult humans, such that a man weighing 73 kg (161 lbs) will have around 3.7 kg (8 lbs) of bone marrow. Human marrow produces approximately 500 billion blood cells per day, which join the systemic circulation via permeable vasculature sinusoids within the medullary cavity. All types of hematopoietic cells, including both myeloid and lymphoid lineages, are created in bone marrow; however, lymphoid cells must migrate to other lymphoid organs (e.g. thymus) in order to complete maturation. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
COVID-19 Pandemic
The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identified in an outbreak in the Chinese city of Wuhan in December 2019. Attempts to contain it there failed, allowing the virus to spread to other areas of Asia and later worldwide. The World Health Organization (WHO) declared the outbreak a public health emergency of international concern on 30 January 2020, and a pandemic on 11 March 2020. As of , the pandemic had caused more than cases and confirmed deaths, making it one of the deadliest in history. COVID-19 symptoms range from undetectable to deadly, but most commonly include fever, dry cough, and fatigue. Severe illness is more likely in elderly patients and those with certain underlying medical conditions. COVID-19 transmits when people breathe in air contaminated by droplets and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
