Health Boards
Fri-01-06-2012, 10:51 AM
Hi Fred,
Sorry I have taken a while to get back to you with information about JAKs and JAK inhibitors but I've been completely off my face on Tramadol for a while and been unable to concentrate on the TV never mind read any papers etc. to get you the info that you need.
The Janus Kinase family of enzymes are tyrosine kinase receptors that are involved in cellular signalling in both cytokine signalling (which recruits cells of your immune system to sites of infection/damage) and apoptosis (the normal, programmed cell death process). They possess a catalytic property and set up a chain of cleavage reactions that send signals to the cellular machinery (DNA, RNA etc) and drive processes within the cells when there is infection and or damage.
In some cases of cancer this cellular signalling pathway has been found to be altered, thus preventing the cells from undergoing apoptosis and and leading them to replicate with their compromised/damaged DNA leading to cancerous tumours. This pathway, when overactive is what leads to the cellular signals that promotes the increased replication of these damaged cells and supression of this pathway in cells where it is "faulty". I would assume that this is where it plays a role in psoriasis too. As we know the cells in psoriasis do not receive the correct signals to stop them from replicating leading to an increased production of skin cells. The immune system also plays a role in psoriasis with the recruitment of faulty T-helper cells to areas of the body which are affected. These faulty T-helper cells do not recognise "self".. which means they see our own cells as foreign and attack the cells in an attempt to rid the body of them. This is thought to be the reason behind the redness and inflammation observed in psoriasis plaques and also one of the main reasons behind the development of psoriatic arthritis.
By inhibiting the JAK-STAT pathway in your cells you can reduce the production of cytokines by immune cells thus lowering the number of cells that are recruited to areas of psoriasis. Cytokines act as signal molecules which can be either locally or systemically (whole body) acting and they recruit a number of different immune function cells in infection but can also act as communication molecules between cells in the same tissue type. By lowering the production of these you lower the communication. Also, by inhibiting the JAK-STAT pathway you also allow cells to undergo the normal process of cell death which, in the case of psoriasis where cells are replicating uncontrolled, this can bring in a level of cell replication control and bring about a reduction in plaques.
Because it's a clinical trial there is not a lot of data out there regarding efficacy. I'll keep an eye on pub med over the next few months to see what I can find.
If you need clarification of anything I have written here (I'm aware it's quite scientific) them please let me know.
Krissie
Sorry I have taken a while to get back to you with information about JAKs and JAK inhibitors but I've been completely off my face on Tramadol for a while and been unable to concentrate on the TV never mind read any papers etc. to get you the info that you need.
The Janus Kinase family of enzymes are tyrosine kinase receptors that are involved in cellular signalling in both cytokine signalling (which recruits cells of your immune system to sites of infection/damage) and apoptosis (the normal, programmed cell death process). They possess a catalytic property and set up a chain of cleavage reactions that send signals to the cellular machinery (DNA, RNA etc) and drive processes within the cells when there is infection and or damage.
In some cases of cancer this cellular signalling pathway has been found to be altered, thus preventing the cells from undergoing apoptosis and and leading them to replicate with their compromised/damaged DNA leading to cancerous tumours. This pathway, when overactive is what leads to the cellular signals that promotes the increased replication of these damaged cells and supression of this pathway in cells where it is "faulty". I would assume that this is where it plays a role in psoriasis too. As we know the cells in psoriasis do not receive the correct signals to stop them from replicating leading to an increased production of skin cells. The immune system also plays a role in psoriasis with the recruitment of faulty T-helper cells to areas of the body which are affected. These faulty T-helper cells do not recognise "self".. which means they see our own cells as foreign and attack the cells in an attempt to rid the body of them. This is thought to be the reason behind the redness and inflammation observed in psoriasis plaques and also one of the main reasons behind the development of psoriatic arthritis.
By inhibiting the JAK-STAT pathway in your cells you can reduce the production of cytokines by immune cells thus lowering the number of cells that are recruited to areas of psoriasis. Cytokines act as signal molecules which can be either locally or systemically (whole body) acting and they recruit a number of different immune function cells in infection but can also act as communication molecules between cells in the same tissue type. By lowering the production of these you lower the communication. Also, by inhibiting the JAK-STAT pathway you also allow cells to undergo the normal process of cell death which, in the case of psoriasis where cells are replicating uncontrolled, this can bring in a level of cell replication control and bring about a reduction in plaques.
Because it's a clinical trial there is not a lot of data out there regarding efficacy. I'll keep an eye on pub med over the next few months to see what I can find.
If you need clarification of anything I have written here (I'm aware it's quite scientific) them please let me know.
Krissie