Glatiramer acetate, often referred to as Glatiramer, is a medication for Multiple Sclerosis (MS). This synthetic compound functions as an immunomodulator, regulating the body’s immune system. Patients typically receive Glatiramer through subcutaneous injections, and it is primarily used to manage relapsing forms of MS. Glatiramer works by influencing immune responses to help mitigate the effects of the disease.
How Multiple Sclerosis Affects the Body
Multiple Sclerosis is an autoimmune disease that targets the central nervous system, encompassing the brain, spinal cord, and optic nerves. In MS, the body’s immune system mistakenly attacks myelin, the protective fatty sheath that insulates nerve fibers. This damage, known as demyelination, disrupts the electrical signals that nerves transmit throughout the body.
This damage leads to the formation of lesions or scars. These lesions impede the proper flow of nerve impulses, causing a wide range of neurological symptoms. Symptoms can include muscle weakness, vision disturbances, numbness, tingling sensations, and problems with coordination. The disease often manifests in periods of new or worsening symptoms, called relapses, followed by periods of remission where symptoms may stabilize or improve.
Glatiramer’s General Mechanism
Glatiramer modulates the immune system by shifting the balance of T-cell responses. This medication is a synthetic mixture of four amino acids—L-alanine, L-lysine, L-glutamic acid, and L-tyrosine—designed to resemble myelin basic protein (MBP), a component of myelin. Glatiramer acts as an “altered peptide ligand” or “decoy” for immune cells.
Glatiramer interacts with antigen-presenting cells (APCs), which display antigens to T cells. This interaction influences how APCs present antigens, leading to a modified T-cell response. The drug encourages the immune system to shift away from a pro-inflammatory Th1 (T helper 1) response, typically associated with autoimmune attacks, towards an anti-inflammatory Th2 (T helper 2) phenotype. This shift is characterized by the production of cytokines, which dampen the immune attack.
Specific Cellular Actions of Glatiramer
Glatiramer binds to Major Histocompatibility Complex (MHC) class II molecules on antigen-presenting cells. This broad binding allows Glatiramer to compete with various myelin antigens for presentation to T cells. This interaction alters the activation of T cells, making them less reactive to myelin components.
Glatiramer induces and expands suppressor T cells, including regulatory T cells (Tregs) and Th2-like cells. These Glatiramer-reactive T cells produce anti-inflammatory cytokines, such as interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-β). Unlike pro-inflammatory cytokines, these molecules help reduce inflammation and suppress the autoimmune response.
These Glatiramer-specific T cells, once activated in the periphery, cross the blood-brain barrier. Inside the central nervous system, they exert localized effects, leading to “bystander suppression.” This means that even if these T cells are not directly attacking myelin, their presence and cytokine release can suppress the activity of other harmful immune cells that are attacking myelin, thereby reducing inflammation and protecting nerve tissue. These cells also express neurotrophic factors like brain-derived neurotrophic factor (BDNF), which promote nerve health and repair.
Translating Mechanism to MS Treatment
The shift in immune response by Glatiramer helps contribute to its therapeutic benefits in MS. By promoting anti-inflammatory Th2 responses and inducing regulatory T cells, the medication reduces inflammatory activity in the central nervous system. This helps to lessen the autoimmune attack on myelin and nerve fibers.
The neuroprotective effects, driven by the release of factors like BDNF, support nerve health and aid in repair processes. The combined impact of reduced inflammation and neuroprotection decreases the frequency of relapses in individuals with relapsing-remitting MS. Over time, this mechanism slows the accumulation of disability and disease progression, managing the chronic nature of MS.