Study Uncovers How Interferon-beta May Be Helping to Treat MS
Treatment helps normalize certain disease-related processes of red blood cells
Researchers have discovered how interferon-beta, a common treatment for multiple sclerosis (MS), may be effective for people with the disease.
Specifically, they found that red blood cells from MS patients have an unusually high ability to bind molecules that contribute to disease-related impairments in neuronal health and myelin repair, compared with cells from healthy people, and that interferon-beta can significantly reduce this ability of red blood cells to bind these molecules.
More studies are needed to better understand interferon-beta’s effects and determine whether its treatment regimen can be optimized based on its newly discovered mechanisms.
The study, “Interferon-β Decreases the Hypermetabolic State of Red Blood Cells from Patients with Multiple Sclerosis,” was published in the journal ACS Chemical Neuroscience.
In MS, the process of repairing the damaged myelin sheath, a protective covering around nerve cell fibers, is impaired. While oligodendrocytes, the cells responsible for myelin repair, go to sites of myelin damage, they do not work properly.
The exact mechanisms behind oligodendrocyte dysfunction remain largely unclear, but these cells are sensitive to nitric oxide and adenosine triphosphate (ATP) — two molecules found at high levels in the blood and brain lesions of people with MS.
Nitric oxide is a potentially harmful gas that promotes oligodendrocyte dysfunction, myelin loss, nerve fiber damage, and cell death. ATP is the primary molecule for storing and transferring energy in cells, and was shown to regulate myelin repair and boost neuroinflammation and neuron susceptibility to damage.
Red blood cells can release nitric oxide directly or stimulate its production in the lining of blood vessels by releasing ATP. When this release occurs in blood vessels nourishing the brain, it may, therefore, promote myelin loss and neuronal damage.
Nitric oxide and ATP release by red blood cells can be promoted by their binding to a complex comprising zinc ion, C-peptide, and albumin. C-peptide is a molecule secreted by the pancreas along with insulin, while albumin, produced by the liver, plays a key role in molecule transport through the blood.
How does interferon-beta work?
Treatments based on the immunomodulatory molecule interferon-beta, such as Rebif (interferon beta-1a) and Betaseron (interferon beta-1b), are commonly used in MS care. While their exact mechanism of action remains incompletely understood, they are thought to modulate immune activity in a way that reduces MS-driving inflammation.
Interferon-beta also binds to zinc, suggesting that its benefits may also be related to a suppression of zinc-red blood cell binding and its subsequent damaging effects.
In the new study, Dana Spence, PhD, a professor of biomedical engineering at Michigan State University, and his team evaluated the effects of interferon-beta on the binding of red blood cells to the albumin/C-peptide/zinc complex.
The researchers first found that red blood cells from MS patients showed a significantly increased binding to all three complex components, compared with those from healthy people. This suggested that the red blood cells of patients have an increased metabolism, or are at a hypermetabolic state.
Treating the patients’ cells with interferon-beta reduced this binding down to normal levels. This was also true for each of the complex components.
Treatment also affected red blood cell function, leading to a significant reduction in ATP release (by 56%) and in GLUT1 levels in their cell membrane (by 24%). GLUT1 is involved in cellular metabolism and promotes ATP release in red blood cells.
Moreover, the team found that albumin boosted zinc and C-peptide binding to red blood cells from MS patients and that this effect was stopped with interferon-beta treatment.
These findings suggest that interferon-beta suppresses albumin binding to red blood cells, “thereby reducing its ability to deliver ligands such as C-peptide and [zinc] to the cell and normalizing the basal hypermetabolic state,” the researchers wrote.
These data may also have implications on the best regimen for interferon-beta administration, the team noted.
“Rather than [under-the-skin] injections that are weeks apart, a daily, less concentrated dose prior to insulin/C-peptide release from pancreatic beta cells would be more appropriate,” the researchers wrote.
The study was funded by the National Institute of Neurological Disorders and Stroke.