Tysabri (Natalizumab) is a promising new drug for the treatment of multiple sclerosis. It is supposed to act by preventing immune cells from entering the brain via the blood-brain barrier. A loss of integrity of the blood-brain barrier is associated with relapses in MS and helping to seal this barrier is one of the mechanisms presumed to underly the beneficial effects of interferon 
It remains to be seen what these unfortunate events will mean for the future of this drug. There is another aspect of the story which I find interesting. If this substance has such powerful effects, positive or negative, can it tell us more about the normal mechanisms of multiple sclerosis or other autoimmune diseases? In particular, what can it tell us about the role of the blood-brain barrier? PML is caused by the JC virus, which is extremely widespread in the human population but usually harmless, causing no symptoms. PML occurs most frequently in patients with AIDS and transplant recipients being treated with drugs which suppress the activity of the immune system. This suggests that under normal circumstances the immune system successfully keeps the virus in check but that when the immune system is suitably impaired the virus can multiply in an uncontrolled way, causing a deadly disease. From this point on it is not hard to imagine a possible connection between drugs which seal the blood-brain barrier and PML. In this scenario the immune system would have been denied sufficient access to the central nervous system to control the virus population.
Natalizumab is a monoclonal antibody against the adhesion molecule VLA-4 (very late antigen 4), also known as CD49, which belongs to the family of integrins and occurs on the surface of leucocytes.
I have not encountered any mathematical models for the function of the blood-brain barrier, despite its importance for many medical issues.
Hydrobates 
August 27, 2008 at 10:49 am |
[…] CNS and causing damage there. Some drugs use to treat MS have the property of sealing the BBB (see the previous post) Breakdown of the BBB has also been suggested to play a role, whether as cause or effect of the […]
November 27, 2014 at 7:13 am |
I just watched a video available from the NIH web site where several scientists describe aspects of a case of PML caused by Natalizumab which ended with the death of the patient. From this I learned some facts about this subject which were new to me. Apparently what is dangerous for the development of PML is not just the presence of the JC virus (which is very common) but the presence of a mutated form. When a patient on Natalizumab gets PML and the drug is removed from the bloodstream by plasmapheresis there is often a dangerous kind of rebound. Immune cells whose access to the CNS is restored stream in in large numbers and cause serious inflammation in the brain. Now some numbers. About 550 patients with MS being treated with Natalizumab have got PML while there is no documented case of a patient with MS not on Natalizumab getting PML. I found this video very interesting since it shows how much can be found out about a case like this under conditions of optimal observation. On the other hand it was quite shocking to see in detail what happens to the brain of someone who is one of the unlucky ones struck by this side effect. There has been progress in recognizing PML but no progress in finding a drug to combat it.