New therapeutic target

[bromley]

Went to Cambridge today for a check-up. As I came out of the lift I bumped into Raven (Robin) - what a small world.

I have now met four posters on this site - Raven, Muu, Loriyas and Jaded. Can anyone beat that?

I never want to meet Lyon (because of the shiny shirts mainly) or Chris55 (who is a sandwich short of a picnic) - just thinking out loud.

I'd like to meet Jimmylegs and Dignan. Maybe HarryZ.


Ian



New therapeutic target for the treatment of multiple sclerosis 22 January 2008

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

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 Zurich (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 published in October in Nature Medicine (1), proved that a certain type of leukocyte, the TH17 lymphocyte, 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 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.

(1) Kebir H., Kreymborg K., Ifergan I., Dodelet-Devillers A., Cayrol R., Bernard M., Giuliani F., Arbour N., Becher B., Prat A. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation (2007). Nat Med, 13(10), 1173-5.

Source: Centre hospitalier de l'Université de Montréal (22/01/08)

[gwa]

I am curious as to how the two of you "found" each other. I assume no pictures had exchanged hands between the two of you prior to the meeting.

gwa

[bromley]

GWA,

Robin posted on this site about Campath and I was considering Campath as a treatment option. I e-mailed him and we met up for a coffee. He invited me to his wedding last year (which I attended). When you are next in London I'll treat you to lunch.

Ian

[Lyon]

.

[gwa]

Bromley,

I will take you up on lunch some day, after you do a tour of London for me and my husband.

gwa

[jimmylegs]

what ho brom old bean!
if brother dignanlegs and i ever make a tour de force of jolly old england we'll be sure to drop in for a spot of tea i like cucumber sandwiches, no preference as regards crusts.
pip pip tally ho sally forth and all that
JL

[raven]

Hey ho Bromley,

Actually you have met 5 board members, my wife is mortified by the fact that she has posted on ThisIsMS and you appear to have forgotten her. I of course reckon it's justified after she forgot to mail your Christmas card! Anyway it was good to run into you and good to see that you're still doing really well.

All the best to Helen

Robin

[dignan]

Sure, cucumber sandwiches are fine, but I'm more interested in a couple of pints of Fuller's.

[HarryZ]

I'd like to meet Jimmylegs and Dignan. Maybe HarryZ.

Maybe??!! Maybe??!! I thought that I would be right up there at the top of the list Then again, perhaps that should be the bottom of the list

Since I'm such a nice guy, I'd even pay for lunch.

Harry

[Muu]

Bromley you old run around- and there i was thinking i was special and not just another notch on your This is Ms bed post. To coin the words of Ms Lewinsky "I feel so disposable!"
(You know I'm joking right?)
Lyon, I'll buy you lunch in London town.
muu