Fingolimod is a medication used to treat multiple sclerosis (MS), a chronic disease affecting the brain and spinal cord. It was the first oral treatment approved for relapsing-remitting multiple sclerosis, offering a new approach compared to injectable therapies. This compound works by influencing the immune system, specifically by reducing the number of certain immune cells that can cause damage in MS. Its development marked a significant step forward in managing this complex neurological condition.
Immune System Basics in Multiple Sclerosis
Multiple sclerosis is an autoimmune disease where the body’s immune system mistakenly attacks its own tissues. In MS, the target of this attack is the myelin sheath, a protective layer that insulates nerve fibers in the central nervous system (CNS), which includes the brain and spinal cord. Myelin allows for rapid and efficient transmission of electrical signals along nerves.
When the myelin sheath is damaged, nerve signals can be disrupted, leading to a wide range of neurological symptoms. Certain immune cells, particularly T lymphocytes and B lymphocytes, play a significant role in this destructive process. These cells, which are normally involved in fighting infections, become overactive and penetrate the CNS, initiating an inflammatory response that strips away myelin. This targeted attack on myelin contributes to the characteristic symptoms and progression observed in MS.
Targeting Sphingosine-1-Phosphate Receptors
Sphingosine-1-phosphate (S1P) is a naturally occurring lipid molecule that plays a part in various biological processes, including the movement of immune cells. S1P exerts its effects by binding to specific proteins on cell surfaces called sphingosine-1-phosphate receptors (S1PRs). S1P1 is particularly involved in immune system regulation.
These receptors are present on a variety of cells, including lymphocytes. Under normal conditions, the interaction between S1P and its S1PRs, especially S1P1, helps regulate the exit of lymphocytes from lymphoid tissues into the bloodstream. This process allows lymphocytes to circulate throughout the body and perform their immune surveillance functions, including entering the central nervous system.
How Fingolimod Alters Immune Cell Movement
Fingolimod, once administered, is converted within the body into an active form called fingolimod-phosphate. This conversion is facilitated by an enzyme. Fingolimod-phosphate structurally resembles natural S1P, allowing it to interact with S1P receptors on lymphocytes.
Specifically, fingolimod-phosphate acts as a functional antagonist at S1P1 receptors found on the surface of T and B lymphocytes. When fingolimod-phosphate binds to these receptors, it causes the S1P1 receptors to be internalized from the cell surface and subsequently degraded. This reduction in available S1P1 receptors prevents lymphocytes from responding to the S1P gradient that normally guides their exit from lymphoid tissues.
As a result, T and B lymphocytes become “trapped” within the lymph nodes. This sequestration prevents these immune cells from entering the general circulation. Consequently, fewer autoimmune lymphocytes are able to cross the blood-brain barrier, which is a protective barrier around the brain and spinal cord, reducing their infiltration into the central nervous system where they would cause inflammation and damage to myelin.
Impact on Disease Progression
The reduced migration of lymphocytes into the central nervous system helps to decrease the inflammatory attacks on myelin. This targeted reduction in inflammation is a primary mechanism by which the drug exerts its therapeutic effects.
The diminished inflammatory activity leads to a decrease in the frequency of MS relapses, which are periods of new or worsening neurological symptoms. Additionally, by protecting the myelin sheath from ongoing immune assault, fingolimod can help slow the accumulation of disability that is characteristic of MS progression. The sequestration of lymphocytes in lymphoid tissues reduces disease activity and preserves neurological function over time.