Potential new approach to the treatment of multiple sclerosis

A prospective new method of treating patients with multiple sclerosis has been proposed by researchers of the Mainz University Medical Center working in cooperation with researchers of the University of Montreal. In model trials and experiments employing human endothelial cells, they discovered that the EGFL7 protein hinders the migration of immune cells into the central nervous system by stabilizing the blood-brain barrier. These findings have recently been published in Nature Communications.

The autoimmune disease multiple sclerosis (MS) is one of the most common disorders that cause disabilities in young adults in industrialized countries. In MS, the body's own immune system attacks the central nervous system (CNS). Immune cells (T cells) cross the blood-brain barrier, i.e., the physiological barrier between the blood circulatory system and the CNS, enter the brain, and damage the protective covering of the nerve fibers, the myelin layer. This results in the degeneration and loss of function of nerve cells and leads to neurological disability-related symptoms.

The primary aim of MS research is to develop new treatments that will prevent this pathological process. Putting the EGFL7 protein at the focus of their research, the team led by Dr. Timo Uphaus and Professor Frauke Zipp of the Department of Neurology at the University Medical Center of Johannes Gutenberg University Mainz collaborated with Dr. Catherine Larochelle of the University of Montreal and Professor Mirko Schmidt and researchers of the German Cancer Consortium (DKTK). They chose a completely innovative pathophysiological-based approach as EGFL7 had not previously been considered of relevance to MS research. However, it has been shown, for example in the case of breast cancer, that EGFL7 does have an influence on the migration of immune cells into tumor tissue. Since the migration of immune cells into the brain plays a significant role in MS, the researchers decided to investigate this protein and whether it could also have an effect on the autoimmune disorder. Notably, on the basis of their results they were able to demonstrate a possible new approach to successfully treat MS.

The researchers discovered that CNS inflammation was accompanied by an increased release of EGFL7. Immune cells subsequently bind to EGFL7, in a sense being taken prisoner so that they are prevented from crossing into the CNS. EGFL7 is released by the endothelial cells of the blood-brain barrier and causes immune cells to be retained in the perivascular space. In their model trials, the researchers next found that exposure to EGLF7 makes the blood-brain barrier less permeable. In the presence of this more effective barrier, the passage of immune cells into the CNS was reduced. This counteracted the corresponding pathological mechanisms and thus led to improvements in clinical symptoms.

Furthermore, the researchers were able to confirm their experimental findings in a human blood-brain barrier model, where there was also decreased migration of immune cells in isolated human endothelial cells. They now conclude that it might be possible in principle to take advantage of the way that EGFL7 inhibits the migration of immune cells into the CNS and enhances the impenetrability of the blood-brain barrier for the treatment of multiple sclerosis.

Catherine Larochelle, Timo Uphaus, Bieke Broux, Elizabeth Gowing, Magdalena Paterka, Laure Michel, Nevenka Dudvarski Stankovic, Frank Bicker, Florent Lemaître, Alexandre Prat, Mirko H. H. Schmidt, Frauke Zipp.
EGFL7 reduces CNS inflammation in mouse.
Nature Communicationsvolume 9, Article number: 819 (2018). doi: 10.1038/s41467-018-03186-z.

Most Popular Now

Sanofi builds focus on rare blood disorders and ca…

Some of the most serious unmet patient needs today are in the field of hematology. Rare blood disorders and blood-related cancers continue to be a major focus of research...

Novartis rises to second place in 2018 Access to M…

Novartis ranked second in the 2018 Access to Medicine Index (ATMi), up from 3rd place in 2016, in recognition of its long-standing efforts to improve worldwide access to ...

FDA approves first treatment for Lambert-Eaton mya…

The U.S. Food and Drug Administration today approved Firdapse (amifampridine) tablets for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults. LEMS is a r...

Pfizer reaches a global agreement with AbbVie

Pfizer Inc. (NYSE:PFE) has signed licensing agreements with AbbVie, resolving all global intellectual property matters for Pfizer's proposed adalimumab biosimilar. Under ...

FDA grants breakthrough device designation to arti…

Bayer announced today that the U.S. Food and Drug Administration (FDA) granted Breakthrough Device Designation to the Artificial Intelligence Software for Chronic Thrombo...

FDA approves new treatment for patients with acute…

The U.S. Food and Drug Administration today approved Daurismo (glasdegib) tablets to be used in combination with low-dose cytarabine (LDAC), a type of chemotherapy, for t...

U.S. FDA approves Larotrectinib, the first TRK inh…

The U.S. Food and Drug Administration (FDA) has approved larotrectinib, the first oral TRK inhibitor, under the brand name Vitrakvi®. The approval is for the treatment of...

GSK reaches agreement to acquire TESARO, an oncolo…

GlaxoSmithKline plc (LSE/NYSE: GSK) and TESARO Inc (NASDAQ: TSRO) announced that the Companies have entered into a definitive agreement pursuant to which GSK will acquire...

Merck and Pfizer provide update on avelumab in pla…

Merck and Pfizer Inc. (NYSE: PFE) today announced that the Phase III JAVELIN Ovarian 200 trial evaluating avelumab* alone or in combination with pegylated liposomal doxor...

Bristol-Myers Squibb awards "Golden Tickets…

Bristol-Myers Squibb Company (NYSE: BMY) and LabCentral, an innovative, shared laboratory space designed as a launchpad for life-sciences and biotech startups, today anno...

Alcon to highlight its vision, strategy and benefi…

Alcon, the eye care division of Novartis, will today hold its first Capital Markets Day for investors and analysts in relation to the previously-announced intention of No...

New study reveals probiotics do not help children …

Probiotics are a multibillion-dollar industry with marketing claims of being an effective treatment for a multitude of ailments, including diarrhea. However, findings fro...