Possible new target for psoriasis treatment found

[Fred]

This study looked at T-lymphokine-activated killer cell-originated protein kinase (TOPK) as a possible new target for treating psoriasis.

Quote:

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Background:
Psoriasis is an inflammatory skin disease. The pathogenesis of psoriasis has not been fully elucidated. T-lymphokine-activated killer cell-originated protein kinase (TOPK) activity increases in a proinflammatory environment, and inhibiting TOPK blocks inflammation. However, whether TOPK is involved in the pathogenesis of psoriasis remains to be identified.

Objectives:
We aimed to study the role of TOPK in psoriasis and attempted to find a drug targeting TOPK for the prevention and treatment of psoriasis.

Method:
Firstly, the expressions of TOPK in psoriatic patients, psoriatic cell and animal model were analysed by Gene Expression Omnibus database, immunohistochemistry (IHC) staining and western blot (WB). After inhibiting TOPK by chemical or gene knockout, the effect of TOPK on the development of psoriasis was verified in cell and animal model by WB, qRT-PCR, ELISA, haematoxylin–eosin (H&E) and IHC staining. Moreover, phosphoproteomic analysis was performed to explore the signalling pathways regulated by TOPK in the occurrence and development of psoriasis. Then, an in vitro kinase assay was performed to prove TOPK kinase activity was inhibited by worenine. Ultimately, WB, qRT-PCR, ELISA, H&E and IHC staining were used to verify the anti-psoriasis effect of worenine by inhibiting TOPK was in cell and animal model.

Results:
In this study, we found that TOPK was highly expressed in psoriasis patients, psoriatic cell and animal model, which suggests that TOPK might be associated with psoriasis pathogenesis. Interestingly, chemical or genetic inhibition of TOPK alleviated M5- and imiquimod (IMQ)-induced psoriasis-like dermatitis, which further confirmed the role of TOPK in promoting the development of psoriasis. Moreover, we determined that worenine inhibited TOPK kinase activity. In addition, worenine relieved M5- and IMQ-induced psoriasiform dermatitis by inhibiting TOPK activity.

Conclusions:
T-lymphokine-activated killer cell-originated protein kinase promotes the development of psoriasis. Therefore, TOPK might be a promising drug target for the prevention and treatment of psoriasis. Worenine alleviates psoriasiform dermatitis by inhibiting TOPK activity, providing new strategies for clinical intervention.

Source: onlinelibrary.wiley.com

*Funding: Health and Family Planning Commission of Hubei Province

[Caroline]

Interesting, perhaps another possible treatment.

Of course we do need to know the role of TOPK in the body… It is there, so there must be a use for it.

What happens if you block it?

It looks like it will alleviate psoriasis.
But there must be something else, the original use and target that also will not function anymore. What is that?

It is again a suppressing treatment, like almost all treatments.

[Fred]

Interesting, perhaps another possible treatment.

Of course we do need to know the role of TOPK in the body… It is there, so there must be a use for it.

What happens if you block it?

It looks like it will alleviate psoriasis.
But there must be something else, the original use and target that also will not function anymore. What is that?

It is again a suppressing treatment, like almost all treatments.

Good point, if we are suppressing are we also blocking some good things. Then again I guess that is the same with all medications.

[Caroline]

Interesting, perhaps another possible treatment.

Of course we do need to know the role of TOPK in the body… It is there, so there must be a use for it.

What happens if you block it?

It looks like it will alleviate psoriasis.
But there must be something else, the original use and target that also will not function anymore. What is that?

It is again a suppressing treatment, like almost all treatments.

Good point, if we are suppressing are we also blocking some good things.  Then again I guess that is the same with all medications.

Yes in almost all medications. Also a TNF blocker, and the IL-inhibitors do that not to mention MTX… That suppresses everything.

Acetretin is different for example, that doesn’t block things, but does have other side effects.

[glenda grant]

Interesting, perhaps another possible treatment.

Of course we do need to know the role of TOPK in the body… It is there, so there must be a use for it.

What happens if you block it?

It looks like it will alleviate psoriasis.
But there must be something else, the original use and target that also will not function anymore. What is that?

It is again a suppressing treatment, like almost all treatments.

Good point, if we are suppressing are we also blocking some good things.  Then again I guess that is the same with all medications. 

Carolyn I certainly agree with you blocking out the bad cells but what happens to our good cells
Don't know what is good about any of my cells the skyrizzi is still working for me thank goodness my insurance pays for it $20,000 a pop! At 4times a year that is $80,000 a year, it's all about money with these pharmaceuticals being so gready. I see there was a glenda grant from georgia not me friends I am not on any boards lucky I can find to find our group

[Kat]

Whenever there is an advertisement for a medication, I always roll my eyes a bit when they say:

"X" is good for this or that disease and will make you fell better. People who are allergic to "X" should not take "X"....

It's like oh really!

I mean isn't it obvious that if you have a known allergy you shouldn't take that particular substance?

Then they list all the bad things that could happen:

This medicine may cause "BAD thing" to happen. 1 in 3 people had "this" happen and the best one...

May cause death.... Um, well yeah that's not how I want to cure my ailment!

So I admit I'm a bit leery of meds and it can be difficult to figure out if it's worth taking it. BUT, meds can be a good life changing thing too so it's not something to just dismiss easily.

And I understand why they warn of the possibilities. Mostly because they are required to do so but even if it's a slim chance, people have the right to know. It's just a bit scary listening to them.

[D Foster]

Looking at the performance of the large pharma companies over the last few years sometimes I think that the main driving force is profit alone and not regard for the person taking the drugs they come up with.

[Kat]

Looking at the performance of the large pharma companies over the last few years sometimes I think that the main driving force is profit alone and not regard for the person taking the drugs they come up with.

It is difficult to know how much trust to put into companies when you know their main concern is going to be money. There are always the good and the bad it seems in everything.