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Nusinersen
Nusinersen, marketed as Spinraza, is a medication used in treating spinal muscular atrophy (SMA), a rare neuromuscular disorder. In December 2016, it became the first approved drug used in treating this disorder. Since the condition it treats is so rare, Nusinersen has so-called "orphan drug" designation in the United States and the European Union. Medical uses The drug is used to treat spinal muscular atrophy associated with a mutation in the ''SMN1'' gene. It is administered directly to the central nervous system (CNS) using intrathecal injection. In clinical trials, the drug halted the disease progression. In around 60% of infants affected by type 1 spinal muscular atrophy, it improves motor function. Side effects People treated with nusinersen had an increased risk of upper and lower respiratory infections and congestion, ear infections, constipation, pulmonary aspiration, teething, and scoliosis. There is a risk that growth of infants and children might be stunted. I ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Spinal Muscular Atrophy
Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting. It is usually diagnosed in infancy or early childhood and if left untreated it is the most common genetic cause of infant death. It may also appear later in life and then have a milder course of the disease. The common feature is the progressive weakness of voluntary muscles, with the arm, leg, and respiratory muscles being affected first. Associated problems may include poor head control, difficulties swallowing, scoliosis, and joint contractures. The age of onset and the severity of symptoms form the basis of the traditional classification of spinal muscular atrophy into a number of types. Spinal muscular atrophy is due to an abnormality (mutation) in the ''SMN1'' gene which encodes SMN, a protein necessary for the survival of motor neurons. Loss of these neurons in the spinal cord prevents signalling between the brain and skeletal mus ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Intrathecal Administration
Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space (sin. ''intrathecal space'') so that it reaches the cerebrospinal fluid (CSF). It is useful in several applications, such as for spinal anesthesia, chemotherapy, or pain management. This route is also used to introduce drugs that fight certain infections, particularly post-neurosurgical. Typically, the drug is given this way to avoid being stopped by the blood–brain barrier, as it may not be able to pass into the brain when given orally. Drugs given by the intrathecal route often have to be compounded specially by a pharmacist or technician because they cannot contain any preservative or other potentially harmful inactive ingredients that are sometimes found in standard injectable drug preparations. Intrathecal pseudodelivery is a technique where the drug is encapsulated in a porous capsule that is placed in communication with the CSF. In t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thrombocytopenia
In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coagulation disorder among intensive care units, intensive care patients and is seen in a fifth of medical patients and a third of surgical patients. A normal human platelet count ranges from 150,000 to 450,000 platelets/microliter (μL) of blood. Values outside this range do not necessarily indicate disease. One common definition of thrombocytopenia requiring emergency treatment is a platelet count below 50,000/μL. Thrombocytopenia can be contrasted with the conditions associated with an abnormally ''high'' level of platelets in the blood – thrombocythemia (when the cause is unknown), and thrombocytosis (when the cause is known). Signs and symptoms Thrombocytopenia usually asymptomatic, has no symptoms and is picked up on a routine comp ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phosphorothioate
Thiophosphates (or phosphorothioates, PS) are chemical compounds and anions with the general chemical formula (''x'' = 0, 1, 2, or 3) and related derivatives where organic groups are attached to one or more O or S. Thiophosphates feature tetrahedral phosphorus(V) centers. Organic Organothiophosphates are a subclass of organophosphorus compounds that are structurally related to the inorganic thiophosphates. Common members have formulas of the type (RO)3−''x''(RS)''x''PS and related compounds where RO is replaced by RS. Many of these compounds are used as insecticides, some have medical applications, and some have been used as oil additives.J. Svara, N. Weferling, T. Hofmann "Phosphorus Compounds, Organic" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2006. Oligonucleotide phosphorothioates (OPS) are modified oligonucleotides where one of the oxygen atoms in the phosphate moiety is replaced by sulfur. They are the basis of antisense therapy, e.g., the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antisense Oligonucleotide
Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small fragments of nucleic acids can be manufactured as single-stranded molecules with any user-specified sequence, and so are vital for artificial gene synthesis, polymerase chain reaction (PCR), DNA sequencing, molecular cloning and as molecular probes. In nature, oligonucleotides are usually found as small RNA molecules that function in the regulation of gene expression (e.g. microRNA), or are degradation intermediates derived from the breakdown of larger nucleic acid molecules. Oligonucleotides are characterized by the sequence of nucleotide residues that make up the entire molecule. The length of the oligonucleotide is usually denoted by " -mer" (from Greek ''meros'', "part"). For example, an oligonucleotide of six nucleotides (nt) is a hexamer, while one of 25 nt ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CYP450
Cytochromes P450 (P450s or CYPs) are a superfamily of enzymes containing heme as a cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for example, they have not been found in ''Escherichia coli''. In mammals, these enzymes oxidize steroids, fatty acids, xenobiotics, and participate in many biosyntheses. By hydroxylation, CYP450 enzymes convert xenobiotics into hydrophilic derivatives, which are more readily excreted. P450s are, in general, the terminal oxidase enzymes in electron transfer chains, broadly categorized as P450-containing systems. The term "P450" is derived from the spectrophotometric peak at the wavelength of the absorption maximum of the enzyme (450 nm) when it is in the reduced state and complexed with carbon monoxide. Most P450s require a protein partner to deliver one or more electrons to reduce the iron (and eventually molecular oxygen). Nomenclature Genes encoding P450 enzymes, and the enzyme ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Exonuclease
Exonucleases are enzymes that work by cleaving nucleotides one at a time from the end (exo) of a polynucleotide chain. A hydrolyzing reaction that breaks phosphodiester bonds at either the 3′ or the 5′ end occurs. Its close relative is the endonuclease, which cleaves phosphodiester bonds in the middle (endo) of a polynucleotide chain. Eukaryotes and prokaryotes have three types of exonucleases involved in the normal turnover of mRNA: 5′ to 3′ exonuclease (Xrn1), which is a dependent decapping protein; 3′ to 5′ exonuclease, an independent protein; and poly(A)-specific 3′ to 5′ exonuclease. In both archaea and eukaryotes, one of the main routes of RNA degradation is performed by the multi-protein exosome complex, which consists largely of 3′ to 5′ exoribonucleases. Significance to polymerase RNA polymerase II is known to be in effect during transcriptional termination; it works with a 5' exonuclease (human gene Xrn2) to degrade the newly formed transcr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Blood Plasma
Blood plasma is a light Amber (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up about 55% of the body's total blood volume. It is the Intravascular compartment, intravascular part of extracellular fluid (all body fluid outside cells). It is mostly water (up to 95% by volume), and contains important dissolved proteins (6–8%; e.g., serum albumins, globulins, and fibrinogen), glucose, clotting factors, electrolytes (, , , , , etc.), hormones, carbon dioxide (plasma being the main medium for excretory product transportation), and oxygen. It plays a vital role in an intravascular osmotic effect that keeps electrolyte concentration balanced and protects the body from infection and other blood-related disorders. Blood plasma can be separated from whole blood through blood fractionation, by adding an anticoagulant to a tube ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cerebrospinal Fluid
Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ventricles of the brain. CSF is mostly produced by specialized Ependyma, ependymal cells in the choroid plexuses of the ventricles of the brain, and absorbed in the arachnoid granulations. It is also produced by ependymal cells in the lining of the ventricles. In humans, there is about 125 mL of CSF at any one time, and about 500 mL is generated every day. CSF acts as a shock absorber, cushion or buffer, providing basic mechanical and immune system, immunological protection to the brain inside the Human skull, skull. CSF also serves a vital function in the cerebral autoregulation of cerebral blood flow. CSF occupies the subarachnoid space (between the arachnoid mater and the pia mater) and the ventricular system around and inside t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Drug Half-life
Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. It is denoted by the abbreviation t_. This is used to measure the removal of things such as metabolites, drugs, and signalling molecules from the body. Typically, the biological half-life refers to the body's natural detoxification (cleansing) through liver metabolism and through the excretion of the measured substance through the kidneys and intestines. This concept is used when the rate of removal is roughly exponential. In a medical context, half-life explicitly describes the time it takes for the blood plasma concentration of a substance to halve (''plasma half-life'') its steady-state when circulating in the full blood of an organism. This measurement is useful in medicine, pharmacology and pharmacokinetics because it helps determi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alternative Splicing
Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene may be included within or excluded from the final RNA product of the gene. This means the exons are joined in different combinations, leading to different splice variants. In the case of protein-coding genes, the proteins translated from these splice variants may contain differences in their amino acid sequence and in their biological functions (see Figure). Biologically relevant alternative splicing occurs as a normal phenomenon in eukaryotes, where it increases the number of proteins that can be encoded by the genome. In humans, it is widely believed that ~95% of multi-exonic genes are alternatively spliced to produce functional alternative products from the same gene but many scientists believe that most of the observed splice variants ar ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SMN2
Survival of motor neuron 2 (''SMN2'') is a gene that encodes the SMN protein (full and truncated) in humans. Gene The ''SMN2'' gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. The telomeric (''SMN1'') and centromeric (''SMN2'') copies of this gene are nearly identical and encode the same protein. The critical sequence difference between the two genes is a single nucleotide in exon 7, which is thought to be an exon splice enhancer. The nucleotide substitution in ''SMN2'' results in around 80-90% of its transcripts to be a truncated, unstable protein of no biological function (Δ7SMN) and only 10-20% of its transcripts being full-length protein (fl-SMN). Note that the nine exons of both the telomer ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
