Une étude publiée dans le numéro de décembre de Nature Medicine apporte des réponses au rôle de
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Une étude publiée dans le numéro de décembre de Nature Medicine apporte des réponses au rôle de

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Press Release New therapeutic target for the treatment of multiple sclerosis Researchers prove the role of certain leukocyte cell adhesion molecules in the pathogenesis of the disease Montréal, January 22, 2007 – A study published in the February issue of Nature Immunology provides answers about the role of novel adhesion molecules in the pathogenesis of multiple sclerosis (MS) and suggests new therapeutic targets for its treatment. The study, by the team of neurologist Dr. Alexandre Prat, neurologist, researcher at the Centre hospitalier de l’Université de Montréal and professor at the Faculty of Medicine of Université de Montréal, reveals that the adhesion molecule, dubbed ALCAM (Activated Leukocyte Cell Adhesion Molecule), or CD166, which is expressed by the endothelial cells of the brain, plays a major role in the migration of certain types of leukocytes to the brain. Researchers believe that the molecule constitutes a novel target to restrict migration of immune cells to the brain, thus dampening neuroinflammation and decreasing the lesions characteristic of MS. MS is a chronic autoimmune disease of the nervous system that affects approximately 55,000 young adults in Canada. Understanding the molecular mechanisms of brain inflammation is essential in the development of new treatments for this degenerative disease. The study was carried out also ...

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Press Release


New therapeutic target for the treatment of
multiple sclerosis

Researchers prove the role of certain leukocyte cell adhesion molecules in the
pathogenesis of the disease


Montréal, January 22, 2007 – A study published in the February issue of Nature Immunology provides
answers about the role of novel adhesion molecules in the pathogenesis of multiple sclerosis (MS) and
suggests new therapeutic targets for its treatment.

The study, by the team of neurologist Dr. Alexandre Prat, neurologist, researcher at the Centre hospitalier
de l’Université de Montréal and professor at the Faculty of Medicine of Université de Montréal, reveals
that the adhesion molecule, dubbed ALCAM (Activated Leukocyte Cell Adhesion Molecule), or CD166,
which is expressed by the endothelial cells of the brain, plays a major role in the migration of certain types
of leukocytes to the brain. Researchers believe that the molecule constitutes a novel target to restrict
migration of immune cells to the brain, thus dampening neuroinflammation and decreasing the lesions
characteristic of MS. MS is a chronic autoimmune disease of the nervous system that affects
approximately 55,000 young adults in Canada.

Understanding the molecular mechanisms of brain inflammation is essential in the development of new
treatments for this degenerative disease. The study was carried out also with researchers at McGill
University (Dr. S. David), Université de Montréal (Dr. N. Arbour), the National Research Council of
Canada (Dr. D. Stanimirovic) and University of Zürich (Dr. B. Becher).

The results clearly demonstrate that CD166/ALCAM is involved in the inflammatory process by priming
the migration of leukocytes across the blood-brain barrier (BBB). The research project combines results
using an in vitro human BBB model and an in vivo experimental autoimmune encephalomyelitis mouse
model. Normally, a limited number of immune cells are able to cross the BBB and penetrate the central
nervous system. In MS and other neuroinflammatory diseases, the increased permeability of the BBB is
associated with an increase in the transmigration of some of these immune cells, which penetrate the
central nervous system and cause the demyelinating lesions of MS. A previous study by Dr. Prat’s team
1published in October in Nature Medicine, proved that a certain type of leukocyte, the T 17 lymphocyte, H
produces two critical products, interleukins 17 and 22 (IL-17 and IL-22), which contribute to infiltrating the
blood-brain barrier and causing inflammation of the central nervous system.

“Blocking the migration of immune cells across the BBB has long been considered a promising
therapeutic approach to autoimmune diseases of the central nervous system,” states Dr. Prat. “This study
has given us new insight into the factors involved in the pathogenesis of immune reactions affecting the

1 Kebir H., Kreymborg K., Ifergan I., Dodelet-Devillers A., Cayrol R., Bernard M., Giuliani F., Arbour N.,
Becher B., Prat A. Human T 17 lymphocytes promote blood-brain barrier disruption and central nervous H
system inflammation (2007). Nat Med, 13(10), 1173-5.

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central nervous system and allowed us to identify potential targets to suppress neuroinflammatory
processes.”


An attractive therapeutic target

Pharmacological agents exist that reduce the transmigration of immune cells by specifically blocking
leukocyte adhesion molecules, thus significantly decreasing the extent of CNS inflammation. However,
they also impede the immune system’s ability to provide protection against chronic viral infections of the
central nervous system, such as progressive multifocal leukoencephalopathy, a demyelinating disease of
the central nervous system caused by the JC virus. Since ALCAM/CD166 blockade does not affect CD8+
T cell migration, whose main function is to destroy cells infected by viruses and neoplastic cells, the study
results suggest that CNS immune protection against viruses would not be compromised by ALCAM
blockade in vivo. ALCAM/CD166 could thus be considered as an attractive therapeutic target for multiple
sclerosis.

This study was funded by the Multiple Sclerosis Society of Canada and by the Canadian Institutes of
Health Research (CIHR).


The blood-brain barrier (BBB)

The BBB is a membranic structure that controls and limits exchanges between the blood and the brain.
Composed of endothelial cells packed tightly within brain capillaries, it maintains the composition of the
brain’s interstitial spaces by its selective and restrictive permeability. It is almost completely impermeable
to various molecules, immune cells and substances circulating in the blood. The BBB thus isolates and
protects the brain from the rest of the organism.


Multiple Sclerosis

In MS, immune cells penetrate the BBB and attack the myelin, a protective sheath that covers the nerve
fibres of the central nervous system. The destruction of myelin causes loss of sensation, paralysis and
handicaps. It is believed that genetic, infectious and environmental factors trigger MS, but the exact
cause of the disease is still unknown. It affects twice as many women as men.


About the Centre hospitalier de l’Université de Montréal (CHUM)
www.chumontreal.qc.ca


About Université de Montréal
www.umontreal.ca


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Sources:
Alexandre Prat, M.D.
Centre hospitalier de l’Université de Montréal
Université de Montréal

Nicole Beaulieu, M.A., APR
Director of Communications
Centre hospitalier de l’Université de Montréal (CHUM)

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Information:
Nathalie Forgue
Communications Advisor
Centre hospitalier de l’Université de Montréal (CHUM)
Tel.: 514 890-8000, extension 14342


Sylvain-Jacques Desjardins
International press attaché
Université de Montréal
Tel.: 514 343-7593
Email: sylvain-jacques.desjardins@umontreal.ca

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