The multiple sclerosis is characterized by chronic inflammation and demyelination of the central nervous system. The etiology of this is disease is still unknown. The genetic and environmental conditions contribute to the pathological studies of the multiple sclerosis.
The multiple sclerosis is an inflammatory disease of the nervous system, i.e., to the brain and spinal cord. Mainly it is related to the white matter tissue of the brain. The white matter of brain consists of nerve fibres that are responsible for the transmission of the signals internally in the brain and the nerves that are supplied into the body from the CNS (Central nervous system).
The multiple sclerosis is classified into different types internationally; Relapsing/remitting multiple sclerosis (RRMS), Primary progressive multiple sclerosis (PPMS), secondary progressive multiple sclerosis (SPMS).
Relapsing/remitting ms (RRMS): Most of the people who are affected with MS are observed to be diagnosed with RRMS. The patients are experienced with series of relapses (exacerbations).the relapses can be last from few days, weeks, or months and the recovery is gradual or instantaneous.
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Graph showing level of disability over time; Showing two different types of RRMS (Source: www.mult-sclerosis.org)
Time (in days)
Primary progressive ms (PPMS): this type of ms is observed in only 10-20% of the total ms affected people. This type of ms is characterized by gradual progression of disease involving declining of the patient's physical abilities with very short periods.
Graph showing level of disability over time; showing two different types of PPMS
Time (in days)
Secondary progressive ms (SPMS): About half of the patients who are suffering with the RRMS will develop SPMS with in a time period of 10years. The SPMS is characterized by the steady clinical damage of nervous system with or without the relapses and minor remissions and plateaus.
Symptoms of the MS: the people with MS are experienced with the partial are complete loss of the functions that are caused by the nervous system, depending on the part of the area which is affected and how much it is affected by the MS. The symptoms vary depending upon the type of MS.
Treatment for multiple sclerosis: there are three groups of disease modifiers are observed till now they are; interferon beta 1a, Glatiramer acetate and Mitoxantrone, a chemotherapeutic agent.
Avonex (Beta interferon-1a):
The interferons produce the biological action by binding to the multi subunit receptors on the surface of the cells. These interferons have inherent enzymatic activity. By the activation of the enzymatic activity in the body that leads to the auto or cross phosphorylation in the receptor subunits, these subunits acts as the docking sites for the cytoplasmic transcription factors. These translocate nucleus and binds to the enhancer elements, by stimulating the gene expression. This interferon signaling cascade is affected by different receptors.
Table showing the list of approved drugs for the treatment of the multiple sclerosis.
Table 1: interferon's approved for MS (11):
Interferon beta 1b
250μg a day
Interferon beta 1a
30μg only once in a weekly
Interferon beta 1a
44μg 3 times in a 7days
The table (2) showing the various types of drugs that are used in the treating Multiple sclerosis.
Table (2): Drugs used in Treatment given for MS (11):
Pharmacology of the drug:
The interferons are a type of glycol-proteins and proteins that are obtained naturally. These are produced in the eukaryotic bacterial cells as a response towards the biological inducers or viral infections that are occurred to the cells. The beta interferon is one among those interferons produced in the eukaryotic cells also produced by different types of cells that include the macrophages and fibroblasts. These naturally occurring interferon beta and beta-1a are glycosylated and now they contain the single N-linked carbohydrate moiety with in them. The process of glycosylation in other type of proteins is affected by differing the stability, aggregation, bio-availability, bio-distribution inside the blood. However the glycosylation effects of the interferon beta-1a and its properties are not properly defined till date.
Mechanism of action of the beta interferons:
Always on Time
Marked to Standard
The beta interferon acts by binding to the type-I interferon receptors, i.e. IFNAR-I and IFNAR2c, which upon the dimerization they activates the JAK (Janus Kinase) and tyro kinases (Jak1 and Tyk2). They transphosphorylate among themselves and also phosphorylates the receptors. Those phosphorylated IFNAR receptors bind to the signal transducers and activators of the transcription (stat-1 and stat-2), which dimerizes themselves and activate the multiple Immuno-modulatory and some antiviral proteins. The beta interferon mostly binds to the type-I interferon receptors than the alpha interferon.
The image showing the mechanism action of interferon beta (39):
Nature of the drug:
Interferon beta is synthetic form of the naturally occurring interferon originated by the recombinant DNA. Currently there are two types of those recombinant beta interferons they are interferon-1a, and interferon 1b which are available for commercial use. The commercial forms of the recombinant interferon preparations are AvonexR and RebifR and for the interferon beta-1b is Betaseron which is a non-glycosylated product obtained from the genetically modified E.coli. These are glycosylated recombinant proteins obtained from Chinese hamster ovarian cells (CHO cells). This CHO cell which has the similar amino acid sequence that of an endogenous human being interferon. The units that measure the potency of the interferon beta are IU (international units), which are being under the WHO guidelines.
The interferon beta is produced by the downstream processing in a bioreactor. The downstream processing encompasses the different steps from cell culturing to final finished product. The protein product that is obtained from the CHO cells is collected from the upstream processing and then several series of steps that takes place in the downstream processing as follows.
Upstream process product
Centrifugation and filtration
Fill and finish
Thus the final interferon is filled in a vial and then sent to the market.