Tuesday, March 8, 2011

The Basics of Benlysta

[Edit: for those who don't know, Benlysta was approved on the 9th of March, 2011. This was written before that happened.]

Benlysta is a monoclonal antibody therapy up for FDA approval this week. If it receives approval it will be the first drug approved specifically for lupus in 50 years. For those with a background in medicine and/or immunology, I recommend this site, which I have found very useful for learning about Benlysta. For those who don’t have a strong background in immunology, I offer the following background information and analogy that I hope will roughly explain how Benlysta works.

Background: The Immune System
            The immune system is very roughly divided into two arms. The first, innate immunity, consists of cells that look for very specific molecules present only on bacteria or other pathogens (aka germs). If these cells “see” those molecules they instantly try to kill the invading pathogen (germ). The good news is that this innate immunity is very quick. The bad news is that it cannot learn anything. The cells will always look for exactly the same molecule(s), and if a pathogen invades the body that doesn’t have the exact molecule(s) the cells are looking for, they won’t “see” it at all.

            The second arm of the immune system is called adaptive immunity. It is composed of B and T cells (collectively called lymphocytes), and is much slower than innate immunity. On the plus side, it can learn and adapt to new threats. B cells and T cells target different kinds of pathogens; for the sake of this explanation we will ignore T cells entirely. We are interested in B cells because they are the only cells in the body that produce antibodies, which generally cause the problems seen in lupus.

When the body is fighting a new pathogen,  the immune system creates a lot of B cells that make randomly generated antibodies that recognize different molecules. Each B cell only makes one kind of antibody, but there are an awful lot of  B cells being made. Eventually the body is going to get lucky and produce a B cell that recognizes molecules on the particular pathogen that it is currently fighting. When that happens the B cell will meet up with the molecule it recognizes, and start producing signals that say, “Yay, I totally recognize this!” and the immune system will then say, “Good for you, start making copies of yourself so that there are lots of antibodies that can attack this pathogen!” In a normal immune system this is good, and the antibodies help get rid of whatever pathogen the body is fighting. In an autoimmune disease these antibodies actually attack the body itself, causing tissue death and inflammation.

Analogy:
           The best analogy I can think of is as follows: Think of a B cell as a soldier in the army; as the war goes on, the soldier will find the particular kind of enemy weapon (s)he is trained to handle. That soldier is going to call back to his commander, and the commander is going to tell the soldier to get to work destroying that weapon. The soldier is then going to do his or her very best to destroy all of the enemy weapons (s)he recognizes in order to help his side win the war.

            In an autoimmune disease, what happens is that the soldier in the above analogy gets confused, and sees one kind of his own side’s weapons as a threat. Not realizing that he is about to destroy his buddies’ weapons, he calls to his commander and says, “Oy! I see a threat!” and of course his commander tells him to get to work destroying it. The soldier (or B cell) dutifully does so, causing damage to his own side (or body). Obviously the soldier needs to be stopped, or  (s)he may cause very serious damage. Most drugs used to treat autoimmune diseases do so by essentially killing enough of the immune system to prevent the confused B cells from destroying parts of the body that they see as foreign. This would be like killing off enough of the collective armed forces (including the navy, air force, etc.) to prevent one soldier in the army from causing problems. These treatments may be effective, but they are not very specific and cause a great deal of collateral damage.

Benlysta:
            Benlysta is much more specific. It targets only B cells, rather than all the cells in the immune system. To extend the analogy, B cells are the army of the immune system. The army has a specific subset of weapons (antibodies) which are used for a specific kinds of targets. In order to keep the confused soldier (B cell) from causing problems, Benlysta jams the radio frequency used by soldiers in the army to communicate with their commanders. This means that the confused soldier (B cell) will still see the thing it thinks is a threat, but will never receive an order to destroy it. The great thing about this is that the rest of the armed forces (or other parts of the immune system) are totally unharmed. They use a different “frequency” to communicate, so Benlysta doesn’t do anything to them. The bad news about Benlysta is that every single army soldier, even the ones that really do see legitimate threats, is jammed, and unable to receive orders from their commander. So Benlysta still knocks out a lot of soldiers (B cells) that could help in the war against real invading pathogens. But at least the navy, airforce, etc. (or other types of cells in the immune system) are still able to fight.

            Even if Benlysta is approved, it will be totally unavailable for a large proportion of lupus patients. This is because it is very, very expensive. All monoclonal antibodies are expensive, for reasons I will try to cover in another post. But even though Benlysta won’t be something that is universally available, it is a good sign that pharmaceutical companies are finally interested in developing drugs for lupus. So let’s hope it passes this last approval process at the  FDA.

4 comments:

  1. You're quite welcome. I hope it was helpful for you.

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  2. I thought Benlysta was approved by the FDA already? Don't know too much about it. I have lupus and would love to hear more about it, when it will be available and who should use it?

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  3. Yes, it was approved 9 March 2011. This was written before that occurred, but I did post something the day it was approved. It should be available soon (within a month or two). I don't know all of the specifications for who is to use it, but I know people must be ANA positive (1:80 or above), must not have neurologic complications and I believe right now they must also not have kidney complications. This is not because Benlysta isn't safe for people with neurologic or kidney problems, just because it hasn't yet been studied in these groups. For the same reason children are not allowed to receive it right now.

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