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Filgotinib (JAK1 inhibitor) future of CFS/ME treatment?

Jesse2233

Jesse2233

Senior Member
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Filgotinib is a Janus kinase inhibitor with selectivity for subtype JAK1 of this enzyme due for release in 2019.

It is rumored that Dr Kenny De Meirleir has his eye on it as a way to break the inflammatory cascade he believes is behind CFS/ME. The drug has also been discussed on various investment forums as a potential CFS/ME treatment.

It is currently undergoing clinical trials for rheumatoid arthritis and Crohn's disease.

Does anyone have more information on this drug? Or have a clear understanding of how its mechanism of action might be helpful?
 
Jesse2233

Jesse2233

Senior Member
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Southern California
More on JAK1
JAK1 is a human tyrosine kinase protein essential for signaling for certain type I and type II cytokines. It interacts with the common gamma chain (γc) of type I cytokine receptors, to elicit signals from the IL-2 receptor family (e.g. IL-2R, IL-7R, IL-9R and IL-15R), the IL-4receptor family (e.g. IL-4R and IL-13R), the gp130 receptor family (e.g. IL-6R, IL-11R, LIF-R, OSM-R, cardiotrophin-1 receptor (CT-1R), ciliary neurotrophic factor receptor (CNTF-R), neurotrophin-1 receptor (NNT-1R) and Leptin-R). It is also important for transducing a signal by type I (IFN-α/β) and type II (IFN-γ) interferons, and members of the IL-10 family via type II cytokine receptors.[5]
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Marc_NL

Marc_NL

Senior Member
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471
Jesse2233 said:
The drug has also been discussed on various investment forums as a potential CFS/ME treatment.
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Do you have a link?
On investment forums I saw it discussed on the official indications mentioned here:
http://www.glpg.com/clinical-pipelines

I've seen it discussed on ME / Lyme forums in relation to ME.



You might also find @Twazzle 's post interesting when he talks about it at the end:
http://forums.phoenixrising.me/inde...ointment-with-dr-kdm.50270/page-5#post-899083


.
 
Jesse2233

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
Marc_NL said:
Do you have a link?
On investment forums I saw it discussed on the official indications mentioned here:
http://www.glpg.com/clinical-pipelines

I've seen it discussed on ME / Lyme forums in relation to ME.



You might also find @Twazzle 's post interesting when he talks about it at the end:
http://forums.phoenixrising.me/inde...ointment-with-dr-kdm.50270/page-5#post-899083


.
Click to expand...

Thanks @Marc_NL

From @Twazzle's post...

"The goal of KDM’s treatment is to attempt to break the cycle which is happening in the intestines by correcting the dysbiosis using pulsed antibiotics/probiotics. In continually removing the source of the inflammation (the excess LPS caused by the SIBO), the immune system over time will allowed a chance to normalise and eventually be able to take care of the problem itself.

This is easier said than done however as the SIBO comes back very quickly after the course of antibiotics, especially in sufferers who have been sick for a long time as the biofilms are better established/there is usually greater degree of inflammation & tight junction breakdown.

There is hope for us all in the future however as a new breed of genetic medicines are due to hit the market in 2019 for Rheumatoid Arthritis/Crohns, if given regulatory approval. They inhibit the JAK enzyme which is responsible for inducing inflammation in the body/gut. The hope is in that inhibiting the JAK 1 /STAT 3 pathway that the dendritic cells in the gut will be extinguished and intestinal immunity will be given chance to normalise. This will attenuate the translocation of LPS, the immune system will shift back to TH1 and systemic inflammation will eventually die down allowing healing/recovery to occur."
 
T

Twazzle

Messages
21
Aubry said:
I heard KDM is going to test this JAK inhibitor on USA patients in 2018 ?
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Where did you hear this?

Also, there is another JAK1 inhibitor drug called upadacinib (AbbieVie) which I have seen is under investigation for numerous inflammatory conditions.

From what I have read it is has a similar effectiveness to filgotinib, although it does express more affinity for JAK2 than filgotinib. This is seen as a negative as inhibiting Jak2 could have a negative impact on hemoglobin and the amount of NK cells which potentially limits the dose. The phase 3 results it has posted so far however (for RA) have been positive.
 
Jesse2233

Jesse2233

Senior Member
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1,942
Location
Southern California
Twazzle said:
Where did you hear this?
although it does express more affinity for JAK2 than filgotinib. This is seen as a negative as inhibiting Jak2 could have a negative impact on hemoglobin and the amount of NK cells which potentially limits the dose.
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Yes JAK2 inhibition seems to be where many of the adverse reported side effects of Tofacitinib (Xeljanz) comes from
 
Daffodil

Daffodil

Senior Member
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5,875
jak1 inhibitor will also likely have a negative impact on NK cell biology, for which some NK booster may be given
 
Aubry

Aubry

Senior Member
Messages
189
Absence of Effects of Filgotinib on Erythrocytes, CD8+ and NK Cells in Rheumatoid Arthritis Patients Brings Further Evidence for the JAK1 Selectivity of Filgotinib
http://acrabstracts.org/abstract/ab...dence-for-the-jak1-selectivity-of-filgotinib/

"Similarly, no effects were observed on blood CD8+and NK cell percentages, suggesting that the gamma chain signalling, mostly dependent on JAK3 signalling, was not inhibited by filgotinib."
 
K

knackers323

Senior Member
Messages
1,625
I tried a small amount and similar to other things that effect the immune system, like Macrolides, Plaquenil etc. I felt much better within hours. Now the question is what is similar to this that is safe to take?
 
justy

justy

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U.K
I'm also hoping i might get a chance to try a Jak inhibitor of some sort, as it is also implicated in MCAS. Its clear to me that a large part of my illness is inflammatory in nature.


Abstract
Mast cell (MC) activation syndrome (MCAS) is a collection of illnesses of inappropriate MC activation with little to no neoplastic MC proliferation, distinguishing it from mastocytosis. MCAS presents as chronic, generally inflammatory multisystem polymorbidity likely driven in most by heterogeneous patterns of constitutively activating mutations in MC regulatory elements, posing challenges for identifying optimal mutation-targeted treatment in individual patients. Targeting commonly affected downstream effectors may yield clinical benefit independent of upstream mutational profile. For example, both activated KIT and numerous cytokine receptors activate the Janus kinases (JAKs). Thus, JAK-inhibiting therapies may be useful against the downstream inflammatory effects of MCAS. The oral JAK1/JAK3 inhibitor, tofacitinib, is currently approved for rheumatoid arthritis and is in clinical trials for other chronic inflammatory disorders. Herein, we report two patients with MCAS who rapidly gained substantial symptomatic response to tofacitinib. Their improvement suggests need for further evaluation of this class of drugs in MCAS treatment.
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https://www.ncbi.nlm.nih.gov/pubmed/28382662
 
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