Therapeutic Antibody Targeting of Indoleamine-2,3-Dioxygenase (IDO2) Inhibits Autoimmune Arthritis, Merlo et al 2017

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466478/

@Jonathan Edwards Given that people with MECFS apparently have mutations in IDO2--do you think using IDO2-specific mAb will work for MECFS as it apparently does for RA? Did this pan out for RA?

 

Summary article

Do you want to treat arthritis? IDO2!

• Joanna Collison

Nature Reviews Rheumatology volume 13, page197(2017)


https://www.nature.com/articles/nrrheum.2017.33

 

Hello,

Bumping this thread with the hope that @Jonathan Edwards might be able to provide comment on this study...Thanks...

 

This is not rheumatoid arthritis. It is some sort of animal disease.
Thousands of drugs improve models like this are useless in humans.
There are no auto reactive T cellist RA so the theory is wrong.
I am afraid this looks like what we used to call the yak dung effect. If you throw yak dung at an experimental animal disease it tends to get better because the immune system is distracted by the yak dung. Doesn't really matter what sort of dung either!

Presumably IDO2 is trendy at the moment so someone has found a way to show targeting it cures arthritis.

If you give a monoclonal like this to a human they will become immune to it within weeks - and what then?

 

I am not sure what this would have to do with ME. And I am not aware of any data showing IDO2 mutations being raised in ME? I thought so far we had no gene linkages.

 

Thanks. IDO2 mutation data from Ron Davis/Robert Phair group--"all 77 patients tested have a mutation in the IDO2 gene, this is "unusual"." I believe this a report of new data.

 

link here

https://www.youtube.com/watch?v=2EhTzwJQNOg

 

Theoretical basis here

The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS

https://www.mdpi.com/2075-4418/9/3/82/htm

 

The entire metabolic trap hypothesis by Robert Phair builds on the idea of damaging IDO2 mutations being a necessary prerequisite to the disease. According to this hypothesis, IDO2 is actually not working and due the peculiar enzyme kinetics of IDO1, patients' cells may get "stuck" with too high tryptophan concentrations and no way to clear it out (due to bistability that makes IDO2 mostly effective at high tryptophan concentrations and IDO1 at lower ones). So targeting IDO2 would do absolutely nothing as a treatment for ME/CFS if it's true that patients already have mutations in IDO2, which make it broken.

 

- Metabolic trap theory: all 77 patients tested have a mutation in the IDO2 gene, this is "unusual".


That does not amount to scientific data in my mind. Just a throw away statement with no background on controls or methodology.

 

Pity this yak dung effect doesn't translate well to humans.