Interferonbeta1a/Humaninterferonbeta1a Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
Launched in the US for relapsing forms of multiple sclerosis (MS), interferon
β-1a is the second compound to be marketed for MS next to interferon p-lb
(Betaseron). This form of p-interferon is a glycosylated polypeptide of 166 amino
acids (sequence identical to human) produced from cultured Chinese hamster ovary
cells containing the engineered human gene for interferon β-1a. The difference in
structure to interferon β-1b lies in the substitution of a cysteine for a serine and in the
fact it is glycosylated. The I b form requires reconstitution and subcutaneous
injection every other day, while the l a form is an intramuscular injection once a week.
The exact mode of action for the β-interferons has not been delineated, however, it is
thought that they reverse a suppressor cell defect and favor the generation of T
helper-2 type responses. It is presumed that the immunoregulatory and antiviral
actions, in addition to the antagonistic effect they have on γ-interferon (γ-interferon
has been shown to exacerbate the symptoms of MS), provide an overall beneficial
effect.
History
The invention of Avonex (interferon beta-1a) began with basic research on interferons, a class of cytokines. The direct development of the drug was led by the biotechnology company Biogen in the 1980s. Utilizing emerging recombinant DNA technology, Biogen scientists inserted the human interferon beta gene into Chinese hamster ovary (CHO) cells for expression. This mammalian cell system was able to perform the correct glycosylation modification of the protein, producing interferon beta-1a with a molecular structure almost identical to that of the human body—a key technological feature. In the subsequent Phase III clinical trial (MSCRG study), weekly intramuscular injections of Avonex were shown to effectively delay disability progression and reduce relapse rates in patients with relapsing-remitting multiple sclerosis (RRMS). Based on these decisive data, Avonex received FDA approval in 1996, becoming the first approved interferon beta-1a drug and establishing its position as a cornerstone of long-term treatment for multiple sclerosis.
Verwenden
Antineoplastic;
biological response modifier.
Allgemeine Beschreibung
Interferon beta-1a (recombinant), Avonex, is a glycoproteinwith 166 amino acids. It has a molecular mass of approximately22,000 Da.Interferon beta-1a is indicated for the treatment of relapsingforms of MS. Patients treated with interferon beta-1ademonstrate a slower progression to disability and a less noticeablebreakdown of the blood-brain barrier as observed ingadolinium-enhanced magnetic resonance imaging (MRI). Although the exact mechanism of action of interferonbeta-1a in MS has not been elucidated, it is known that thedrug exerts its biological effects by binding to specific receptorson the surface of human cells. This binding initiatesa cascade of intracellular events that lead to the expressionof interferon-induced gene products.
Adverse effects include flulike syndrome at the start oftherapy that decreases in severity as treatment progresses.Interferon beta-1a is a potential abortifacient and an inhibitorof cytochrome P450.The dosage form is a powder for solution that is reconstitutedin sterile water. Excipients are human albumin,sodium chloride, and phosphate buffer.
Interferonbeta1a/Humaninterferonbeta1a Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
