Tissue Selectivity of S1P Receptor Modulator


Krzysztof Selmaj, MD, PhD, explains the tissue selectivity of sphinogine-1-phospate (S1P) receptor modulators and the clinical considerations that arise when treating multiple sclerosis (MS).


Krzysztof Selmaj, MD, PhD: The difference between nonselective S1P receptor modulators and selective ones depends on the target equal number of types of S1P receptors and the tissue distribution of S1P receptors. They’re expressed widely in many tissues, expressing that immune tissue in the immune system and effecting the S1P receptor modulators on immune cells. They present 1 of the major mechanisms of action in multiple sclerosis [MS]. One of the primary effects it has on the immune system is changing trafficking of human cells among different lymphatic organs. They control egress of lymphocytes from the lymph nodes, leading to a decreased number of lymphocytes in the circulation, including a diminishing number of autoimmune cells in circulation. In this way, they contribute to the benefit effect in multiple sclerosis.

But S1P receptor modulators are also expressed in several other tissues. Another important location is the heart because it’s related to potential adverse effects from treating patients with S1P receptor modulators. They express in the heart muscle cells and in the conduction tissue in the heart. They can influence the heart rate. They can lead to tachycardia and potentially go after ventricular blocks. All are important events in the treatment of patients with MS with S1P receptor modulators. In addition, S1P receptors are expressed in the liver and contribute to the liver function. Because of that, we can expect some involvement of S1P receptor modulators in liver function and some adverse effects related to the liver function.

Apart from that, the important thing is that S1P receptor modulators are expressed in the brain, which is the home organ for multiple sclerosis. There’s a wide expression of these receptors on various endogenous cells to CNS [central nervous system], like astrocytes, neurons, and oligodendrocytes. The oligodendrocytes are the cells directly linked to myelination and the selection of myelin and directly involved in the mechanisms of multiple sclerosis. Interestingly enough, in this case, with its interaction with oligodendrocytes, S1P receptor modulators support the function of cells, contribute to the maintenance of myelin, and to some extent prevent the destruction of myelin during the pathogenic process of MS.

Another location of S1P receptors is the eyes, especially the macula. It’s related to the influence on the permeability of blood fluids in the retina. One potential adverse effect of S1P receptor modulators is macular edema, which is a lot of complication that’s not rare but typical. This receptors are also expressed in lungs. There are some effects on lung function, but not many. Initially, it was thought to be bigger, but now we know it’s not particularly big. But they can also change their function of lungs, and they can sometimes contribute to hyperactivity of lung function. This is the major distribution of S1P receptor modulators. They have a wide presence, and they can affect several biological functions in the body.

Transcript edited for clarity.

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