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Vamorolone is a corticosteroid approved by the FDA for the treatment of Duchenne Muscular Dystrophy. The brand name of Vamorolone is Agamree. Santhera Pharmaceuticals received the approval for Agamree on October 26, 2023. Duchenne Muscular Dystrophy is a muscular disorder caused by dysfunctional Dystrophin that over time causes weakening of muscles. We will see what is dystrophin and why it is so important in muscle movement. Vamorolone is a corticosteroid that exerts anti-inflammatory and immunosuppressive effects. In this article, we will see what is Duchenne Muscular Dystrophy, the mechanism of action of Vamorolone, and adverse affects / side effects of Vamorolone / Agamree.
There are several more medicines approved by the FDA in the year 2023. We have written articles on some of them like
What is Duchenne Muscular Dystrophy
- We can move our body parts because of muscle contraction. Muscles are made up of long, tubular cells called “Myocytes”.
- Dystrophin is present near the membrane of myocytes. Dystrophin connects the Actin cytoskeleton inside the myocyte with the extracellular matrix present outside the myocyte. This linkage protects the myocyte membrane when our muscles contract.
- Dystrophin has three important areas: 1) the Actin-binding end which attaches to the actin cytoskeleton, 2) the central rod, and 3) the Dystroglycan-binding end which attaches to Dystroglycan complex which is present in the myocyte membrane and is in direct contact with the extracellular matrix.
- Sometimes, due to genetic mutation, Dystrophin is shorter than normal and often lacks a Dystroglycan-binding end. This is the root cause of Duchenne Muscular Dystrophy.
- Since dystrophin is important in protecting myocyte membrane, a dysfunctional dystrophin makes the membrane vulnerable to tears.
- So, whenever the muscle contracts, small rips appear in the myocyte membrane.
- These small rips allow the diffusion of various molecules in and out of the myocyte membrane.
- Calcium ions are present outside of the myocyte and now can move inside due to these small rips.
- These Calcium ions activate the protease enzyme which is responsible for breaking down proteins.
- Proteases are used only for breaking down damaged proteins. However, due to extra calcium causing unwanted activation of proteases, some important muscle proteins get broken down. This eventually kills the myocyte.
- Creatine kinase is present inside the myocytes but because of these rips, it also diffuses out of myocytes causing high serum levels of Creatine kinase. Therefore, creatine kinase levels are an indicator to detect Duchenne Muscular Dystrophy.
- Creatine kinase is used to store energy in the myocytes to use during the contraction. However, due to this leakage of creatine kinase, less energy is stored in the myocyte. This eventually weakens the muscles.
- Fat and scar tissues start to fill the gap of myocyte which further weakens the muscle.
Mechanism of Action of Vamorolone
- The exact mechanism by which vamorolone reduces inflammation in the context of Duchenne muscular dystrophy (DMD) is not fully elucidated. However, vamorolone is designed to have anti-inflammatory effects while aiming to minimize some of the side effects associated with traditional corticosteroids.
- Vamorolone acts through the glucocorticoid receptor, a protein involved in the cellular response to stress and inflammation. Unlike traditional corticosteroids, vamorolone is believed to have a different binding profile to the glucocorticoid receptor. This may lead to a more selective modulation of the receptor, potentially allowing for anti-inflammatory effects with fewer side effects.
- Vamorolone may influence immune cells involved in the inflammatory response. By modulating the activity of immune cells, it could potentially reduce their contribution to inflammation in muscle tissue.
- Traditional corticosteroids, while effective at reducing inflammation, can have side effects such as bone loss, growth retardation, and immune suppression. Vamorolone is designed to mitigate some of these side effects through its unique binding properties to the glucocorticoid receptor.
Adverse Effects or Side Effects of Vamorolone
- Alterations in Endocrine Function
- Immunosuppression and Increased Risk of Infection
- Alterations in Cardiovascular/Renal Function
- Gastrointestinal Perforation
- Behavioral and Mood Disturbances
- Effects on Bones
- Ophthalmic Effects
- Immunizations
- Effects on Growth and Development
- Myopathy
- Kaposi’s Sarcoma
- Thromboembolic Events
- Anaphylaxis
