Nav: Home

An antibody-based drug for multiple sclerosis

July 19, 2016

Inserm Unit U919, directed by Prof. Denis Vivien ("Serine Proteases and Physiopathology of the Neurovascular Unit") has developed an antibody with potential therapeutic effects against multiple sclerosis. The study, directed by Fabian Docagne and published in Brain, paves the way for a new strategy to control the disease.

Multiple sclerosis is a disease that affects the central nervous system, particularly the brain and spinal cord. It is the most common cause of neurological disability in young adults.

The disease is considered autoimmune since the immune system, which is there to protect the body from external assault, attacks its own constituents. The cells of the immune system, particularly the lymphocytes, bring about the destruction of the myelin sheath that surrounds and protects the extensions (axons) of the neurons. This demyelination, which marks the beginning of axon degeneration, disrupts the transmission of nerve impulses. Lesions in the form of "plaques" are dispersed over the brain and spinal cord. They cause symptoms that vary greatly from one individual to another.

Usually, the disease is characterised by exacerbations, with the appearance of motor, sensory and cognitive disorders, followed by remission a few weeks later. But with the passage of years, these symptoms can progress to irreversible disability. Current treatments reduce the exacerbations and improve the quality of life of patients, but do not control the progression of the disease.

In order for the cells of the immune system circulating in the bloodstream to reach the central nervous system, they must penetrate the blood-brain barrier (haematoencephalic barrier) and blood-spinal cord barrier (haematomedullary barrier).

During previous work on a mouse model of stroke, the team from Inserm Unit 919 studied a factor involved in opening the blood-brain barrier, the NMDA receptor. In particular, they observed that blocking the interaction of this receptor with tPA (a member of the serine protease family) has beneficial effects associated with maintaining the integrity of the barrier.

In this study, the researchers developed a strategy for blocking the interaction of tPA with the receptor, in multiple sclerosis. In the laboratory, they developed a monoclonal antibody (Glunomab®) directed against the specific site on the NMDA receptor to which tPA binds.

In cellular models of the human blood-brain and blood-spinal cord barriers, the use of this antibody prevented opening of the barrier under inflammatory conditions, limiting the entry of lymphocytes. The team then tested the therapeutic effects of the antibody in an experimental mouse model of multiple sclerosis. After intravenous injection of Glunomab, the progression of motor disorders (partial or total paralysis of the limbs), as assessed by a clinical score, was blocked. In these treated mice, this effect was associated with reduced infiltration of lymphocytes into the nervous tissue, and reduced demyelination. By thus preventing myelin destruction by the cells of the immune system, this strategy might represent a promising therapy for the control of multiple sclerosis.

A patent application has been filed on this work.
-end-
Sources

Neuroendothelial NMDA receptors as therapeutic targets in experimental autoimmune encephalomyelitis
R. Macrez1, M.C. Ortega2, I. Bardou1 , A. Mehra1 , A. Fournier1 , S.M.A. Van der Pol3 , B. Haelewyn4 , E. Maubert1 , F. Lesept1,5, A. Chevilley1 , F. de Castro2,6, H.E. De Vries3 , D. Vivien1 , D. Clemente2,7 and F. Docagne1

1 INSERM, INSERM-U919, Caen Cedex, F-14074 France; Université de Caen Basse-Normandie, Caen Cedex, F-14074 France; GIP Cyceron, Caen, F-14074 France.
2 Grupo de Grupo de Neurobiología del Desarrollo-GNDe. Hospital Nacional de Parapléjicos - Toledo, Spain.
3 Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, The Netherlands.
4 Centre Universitaire de Ressources Biologiques, Université de Caen Basse-Normandie, Caen, France.
5 Present address: Department of Neuroscience, Physiology and Pharmacology, University College of London, United Kingdom.
6 Grupo de Neurobiología del Desarrollo-GNDe. Instituto Cajal. CSIC - Madrid, Spain.
7 Grupo de Neuroimmuno-reparación. Hospital Nacional de Parapléjicos - Toledo, Spain.

Funded by ARSEP Foundation and the French Medical Research Foundation (FRM)

Brain, 20th July 2016

Investigator contact

Fabian Docagne
Fabian Docagne, PhD
Inserm Unit U919 "Serine Proteases and Physiopathology of the Neurovascular Unit" (SP2U), Cyceron Centre
Tel.: +33 (0)2 31 47 01 02
Email: docagne@cyceron.fr

INSERM (Institut national de la santé et de la recherche médicale)

Related Immune System Articles:

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.
Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.
How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.
Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
First impressions go a long way in the immune system
An algorithm that predicts the immune response to a pathogen could lead to early diagnosis for such diseases as tuberculosis
Filming how our immune system kill bacteria
To kill bacteria in the blood, our immune system relies on nanomachines that can open deadly holes in their targets.
Putting the break on our immune system's response
Researchers have discovered how a tiny molecule known as miR-132 acts as a 'handbrake' on our immune system -- helping us fight infection.
Decoding the human immune system
For the first time ever, researchers are comprehensively sequencing the human immune system, which is billions of times larger than the human genome.
Masterswitch discovered in body's immune system
Scientists have discovered a critical part of the body's immune system with potentially major implications for the treatment of some of the most devastating diseases affecting humans.
More Immune System News and Immune System Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Our Relationship With Water
We need water to live. But with rising seas and so many lacking clean water – water is in crisis and so are we. This hour, TED speakers explore ideas around restoring our relationship with water. Guests on the show include legal scholar Kelsey Leonard, artist LaToya Ruby Frazier, and community organizer Colette Pichon Battle.
Now Playing: Science for the People

#569 Facing Fear
What do you fear? I mean really fear? Well, ok, maybe right now that's tough. We're living in a new age and definition of fear. But what do we do about it? Eva Holland has faced her fears, including trauma and phobia. She lived to tell the tale and write a book: "Nerve: Adventures in the Science of Fear".
Now Playing: Radiolab

Uncounted
First things first: our very own Latif Nasser has an exciting new show on Netflix. He talks to Jad about the hidden forces of the world that connect us all. Then, with an eye on the upcoming election, we take a look back: at two pieces from More Perfect Season 3 about Constitutional amendments that determine who gets to vote. Former Radiolab producer Julia Longoria takes us to Washington, D.C. The capital is at the heart of our democracy, but it's not a state, and it wasn't until the 23rd Amendment that its people got the right to vote for president. But that still left DC without full representation in Congress; D.C. sends a "non-voting delegate" to the House. Julia profiles that delegate, Congresswoman Eleanor Holmes Norton, and her unique approach to fighting for power in a virtually powerless role. Second, Radiolab producer Sarah Qari looks at a current fight to lower the US voting age to 16 that harkens back to the fight for the 26th Amendment in the 1960s. Eighteen-year-olds at the time argued that if they were old enough to be drafted to fight in the War, they were old enough to have a voice in our democracy. But what about today, when even younger Americans are finding themselves at the center of national political debates? Does it mean we should lower the voting age even further? This episode was reported and produced by Julia Longoria and Sarah Qari. Check out Latif Nasser's new Netflix show Connected here. Support Radiolab today at Radiolab.org/donate.