Multiple Sclerosis Drug Works in a Surprising Way

Summary: Interferon betas, a class of drugs commonly prescribed to those with multiple sclerosis reduces the binding of zinc, C-peptide, and albumin to red blood cells.

Source: ACS

Drugs called interferon betas are common treatments for multiple sclerosis (MS), reducing relapses and slowing motor function decline. Interferon beta, a protein known to contain a zinc binding pocket, is thought to reduce proinflammatory molecules and even increase production of anti-inflammatory species in MS patients.

But researchers now report in ACS Chemical Neuroscience that the molecule reduces the binding of three components—zinc, C-peptide and albumin—to red blood cells.

According to the National Multiple Sclerosis Society, almost a million people in the U.S. and about 2.8 million people worldwide live with MS.

This autoimmune disease damages the myelin sheath, an insulating layer of proteins and fats wrapped around nerves, which leads to impaired neuronal signaling. People with MS typically have pain, numbness and mobility issues that worsen over time.

Cells that make myelin are sensitive to adenosine triphosphate (ATP) and nitric oxide (NO), molecules that are present in high amounts in the blood and brain lesions of MS patients. Red blood cells can release NO directly, but they can also stimulate NO production in the lining of blood vessels by releasing ATP.

This shows a brain
Cells that make myelin are sensitive to adenosine triphosphate (ATP) and nitric oxide (NO), molecules that are present in high amounts in the blood and brain lesions of MS patients. Image is in the public domain

NO can then go on to damage nerves in MS patients. Zinc, C-peptide—which is secreted by the pancreas along with insulin—and albumin are key players in the latter process, and they can latch onto red blood cells.

Because interferon beta can bind zinc, it seemed possible that the drug helped patients by sopping up this mineral, so Dana Spence and colleagues wanted to investigate further.

In lab tests, the researchers found that red blood cells from MS patients bound more zinc, C-peptide and albumin than cells from control subjects. Treatment with interferon beta reduced this interaction in MS samples down to control levels.

Albumin boosted zinc and C-peptide binding to MS red blood cells, and this effect went away with interferon beta treatment.

From these data, the researchers conclude that it’s likely the drug is inhibiting albumin binding, keeping it from delivering its cargo of C-peptide and zinc to red blood cells so that NO can be made.

About this neuropharmacology research news

Author: Press Office
Source: ACS
Contact: Press Office – ACS
Image: The image is in the public domain

Original Research: Closed access.
Interferon‑β Decreases the Hypermetabolic State of Red Blood Cells from Patients with Multiple Sclerosis” by M. Jacobs et al. ACS Chemical Neuroscience


Abstract

Interferon‑β Decreases the Hypermetabolic State of Red Blood Cells from Patients with Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory disease characterized by damage to the myelin sheath surrounding axons in the central nervous system. While the exact mechanism of this destruction is unknown, excess nitric oxide (NO) and adenosine triphosphate (ATP) have been measured in tissues and fluids obtained from people with MS.

Here, incubation of interferon-beta (IFN-β), an MS drug with an unknown mechanism of action, with red blood cells (RBCs) obtained from people with MS provide evidence of a potential hypermetabolic state in the MS RBC that is decreased with IFN-β intervention.

Specifically, binding of all three components of an albumin/C-peptide/Zn2+ complex to MS RBCs was significantly increased in comparison to control RBCs. For example, the binding of C-peptide to MS RBCs was significantly increased (3.4 ± 0.1 nM) compared to control RBCs (1.6 ± 0.2 nM). However, C-peptide binding to MS RBCs was reduced to a value (1.6 ± 0.3 nM) statistically equal to that of control RBCs in the presence of 2 nM IFN-β.

Similar trends were measured for albumin and Zn2+ binding to RBCs when in the presence of IFN-β. RBC function was also affected by incubation of cells with IFN-β. Specifically, RBC-derived ATP and measurable membrane GLUT1 were both significantly decreased (56 and 24%, respectively) in the presence of IFN-β.

Collectively, our results suggest that IFN-β inhibits albumin binding to the RBC, thereby reducing its ability to deliver ligands such as C-peptide and Zn2+ to the cell and normalizing the basal hypermetabolic state.

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