Research with Rats Finds Possible New Treatment for AAV

by Danielle Bradshaw from In The Cloud Copy

It has been found that fingolimod – a drug typically used for multiple sclerosis – may also be effective in treating ANCA-associated vasculitis (AAV), as shown by a study conducted with rats.

What Is AAV?

AAV is essentially inflammation of the blood vessels. It is an autoimmune response wherein a person’s immune system creates auto-antibodies, which in the case of ANCA-associated vasculitis, attack a particular kind of white blood cells called neutrophils.

What causes the blood vessels to inflame is the neutrophils migrating through the vessels. It can be likened to a hurried evacuation that results in inflammation and vascular damage. AAV isn’t a very common illness as it affects around 1 in every 50,000 people. It’s much more likely to be found in middle-aged Caucasians.

Is There a Secret to Managing AAV?

It has been theorized that the lipid (fat molecule) sphingosine-1 phosphate (or S1P) can be regulated by certain medications. S1P’s job is to oversee much of what goes on inside of your body by attaching itself to distinct protein receptors.

S1P happens to be able to help mitigate inflammation by telling immune cells where to go. Scientists and researchers built off of that information and came to the conclusion that some already existing drugs, like fingolimod (or Gilenya, as sold by Novartis) could help manage AAV as it works by adjusting the behavior of S1P.

Conducting the Study

With this information in mind, a team of researchers in China wanted to see just how effective fingolimod really can be for relieving AAV associated complications. The team did this by constructing a trial with rats capable of producing the aforementioned ANCA antibodies.

To make it possible for the rats to produce these antibodies (also called MPO-ANCA antibodies) they were inoculated with myeloperoxidase, which is a protein found inside of people. These particular antibodies then seek out immune cells and damage the vascular system.

During the course of the study, the rats began to have heightened levels of protein and blood in their urine which is an indication of kidney damage. After around four weeks, the rats AAV diagnosis was well documented and they were put on a fingolimod regiment five days out of the week.

The drug was shown to lessen lung and kidney damage – the parts of the body most affected by AAV. The rats that were undergoing fingolimod treatments had a lower percentage of glomerular crescents (indicators of kidney damages). The rats that were given a placebo had a much higher amount of these glomerular crescents.

The fingolimod is able to or is at least believed to – trap immune cells inside of lymph nodes so that they aren’t able to move throughout the body to cause swelling. It is thought that this is what lowered the number of immune cells, T-cells in this case, inside of the rat’s kidneys.

Further experimentation with cells showed that the medication can diminish the growth of T-cells and lower the risk of them traveling through tissue and blood. The research team did, however, find that fingolimod didn’t have much of an impact on the ANCA antibodies themselves.

Members of the research team have stated that fingolimod was shown to be an effective treatment within their rat model. The treatment works by limiting the number of T-cells within the kidneys and lowering the production of T-cells and limiting their movement inside the body. Fingolimod may be a potentially useful therapy for AAV.

Check out the original story here.

The study can be found here.

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