One way the body may protect itself from nerve cell inflammation is to have cells in the blood-brain barrier increase their production of a protein that keeps immune cells from entering the brain, researchers in Germany and Canada report.
The finding suggests that scientists could develop a multiple sclerosis therapy around the protein, known as EGFL7. It would work by preventing as many inflammation-generating immune cells from entering the brain.
The underlying trigger for MS is immune cells crossing the blood-brain barrier to invade the central nervous system (CNS). The barrier is a selective membrane that shields the CNS from general blood circulation.
But “as with other highly effective disease-modifying therapies which influence a broad range of peripheral immune cells, potential devastating adverse events limit the use of this therapy as a first-line agent,” the researchers wrote.
The team at Mainz University Medical Center in Germany and the University of Montreal wondered if epidermal growth factor-like protein 7 (EGFL7) could prevent the brain inflammation in MS. Although scientists had not previously linked it to MS, it was shown to regulate the migration of immune cells into breast cancer tumors.
The CNS response to the chronic inflammation seen in MS patients and a mouse model of the disease was to increase EGFL7 in the blood-brain barrier, the researchers found.
Researchers said the increase prevented pro-inflammatory immune cells from crossing into the CNS. Endothelial cells that line blood capillaries in the blood-brain barrier are the ones that secrete EGFL7.
“We postulate that EGFL7 upregulation by BBB-ECs [brain blood barrier-endothelial cells] is induced as a compensatory mechanism to promote survival and recovery of BBB function in neuroinflammatory conditions,” the team wrote.
Researchers then tested what happened in mice that lacked EGFL7. They found that the mice developed MS earlier and that their blood-brain barrier membrane was less efficient at keeping immune cells out. Treatment with EGFL7 improved the disease severity in the MS mice and tightened the blood-brain barrier, they said.
“In light of our findings, smaller EGFL7 agonists, in development for other diseases, could therefore constitute an appealing therapeutic avenue for MS,” the team concluded.