Kynurenine skal afprøves til behandling af ME patienter

Open Medicine Foundation finansierer et nyt placebo-kontrolleret studie, hvor ME patienter skal behandles med kynurenine:

Kynurenine Clinical Trial for ME/CFS
https://omfcanada.ngo/kynurenine-clinical-trial-for-me-cfs/

Jonas Bergquist, MD, PhD, direktør for det svenske ME/CFS forskningscenter i Uppsala, skal stå for studiet.

Baggrunden for studiet er Dr. Robert Phair's ME- hypotese "den metaboliske fælde", der beskriver, at ME patienter ikke omsætter aminosyren tryptofan i tilstrækkelig omfang i nogle af vores celletyper (1). Blogindlæg om den metaboliske fælde:

ME hypotese: The Metabolic Trap - den metaboliske fælde
https://followmeindenmark.blogspot.com/2019/06/me-hypotese-metabolic-trap-den.html

Kynurenine metabolitter opstår ved omsætning af tryptofan, og disse metabolitter er vigtige for normal funktion af bl.a. hjerne og immunforsvar. Dette er vist i dette blogindlæg: 

Tryptofan metabolitten kynureninsyre har immunmodulerende egenskaber
https://followmeindenmark.blogspot.com/2019/06/tryptofan-metabolitten-kynureninsyre.html


Yderligere blogindlæg om kynurenine og den metaboliske fælde:

Is the ME hypothesis "the metabolic trap" able to explain endothelial dysfunction?
https://followmeindenmark.blogspot.com/2019/06/is-me-hypothesis-metabolic-trap-able-to.html

Kynurenine metabolisme påvirkes af motion
https://followmeindenmark.blogspot.com/2019/06/kynurenine-metabolisme-pavirkes-af.html

Omsætning af tryptofan og forgrenede aminosyrer hos ME patienter under motion
https://followmeindenmark.blogspot.com/2019/06/omstning-af-tryptofan-og-forgrenede.html

Is the kynurenic acid responsive Gpr35 involved in the ME pathomechanism?
https://followmeindenmark.blogspot.com/2019/06/is-kynurenic-acid-responsive-gpr35.html

IDO-ME hypotesen er forenelig med AHR-MCS hypotesen
https://followmeindenmark.blogspot.com/2019/06/ido-me-hypotesen-er-forenelig-med-ahr.html

Mutations in the IDO2 gene and DNA methylations in genes in the NAD/NADP synthesis pathway in ME
https://followmeindenmark.blogspot.com/2019/07/mutations-in-ido2-gene-and-dna.html

Reference: 
1) Kashi AA Davis RW and, Phair RD: The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS. Diagnostics (Basel). 2019 Jul 26;9(3). pii: E82. doi: 10.3390/diagnostics9030082. https://www.mdpi.com/2075-4418/9/3/82

Serum fra ME patienter udviser antiviral aktivitet

Et nyt studie af Schreiner et al har vist, at serum fra ME patienter udviser antiviral aktivitet mod både DNA- og RNA-virus i en cellekultur. Samtidig blev det observeret, at serummet inducerer et fragmenteret mitokondriel netværk og nedsat cellulær ATP produktion (1).

Citat fra artiklen (1), side 213: 
"... we showed that serum from ME/CFS patients contained an activity that produced mitochondrial fragmentation, decreased mitochondrial ATP production, and induced a powerful antiviral state."

Det er ukendt, hvad det er i serum, som udløser og udøver den antivirale aktivitet. Schreiner et al har en hypotese om, at en delvis aktivering af herpesvirus (HHV-6) kan være årsag til den kroniske immunaktivering hos ME patienter. Forskerne understøtter hypotesen med et forsøg, hvor en cellekultur udsat for delvis aktivering af HHV-6 udskilder et stof som har samme effekt som serum fra ME patienter (1). 

Citat fra artiklen (1), side 206:
"...These results showed that cells containing latent HHV-6A DNA that had been transactivated by TSA (trichostatin-A) secreted a potent activity that could be adoptively transferred and induce mitochondrial fragmentation and a proinflammatory CDR (cell danger response) in naive responder cells, conferring strong protection from both DNA and RNA virus infections."

ME er tidligere sat i forbindelse med kronisk herpes infektion (2).

Schreiner et al foreslår, at nye forsøg skal vise om ME patienter har en produktion af HHV-6 proteiner (ikke hele, levende HHV-6).

Citat fra artiklen (1), side 213:
"Larger multicohort studies involving ME/CFS patients from different age groups should be carried out in the future and should include methods for detecting and quantifying both productive and nonproductive (incomplete) viral reactivation events. Furthermore, potential factors affecting mitochondrial dynamics in ME/CFS patients should be systematically evaluated for their ability to induce a powerful antiviral state."

Læs også:

For ME/CFS Patients, Viral Immunities Come at a Devastating, Lifelong Cost
https://health.ucsd.edu/news/releases/Pages/2020-04-27-for-me-cfs-patients-viral-immunities-come-at-lifelong-cost.aspx

Explaining ME/CFS? Prusty / Naviaux Study Ties Infections to Energy Breakdowns
https://www.healthrising.org/blog/2020/04/26/explaining-chronic-fatigue-syndrome-naviaux-prusty/

Viden om fragmenteret mitokondriel netværk:
Mitochondria in Innate Immune Responses
https://pubmed.ncbi.nlm.nih.gov/21597473/

Figur: https://pubmed.ncbi.nlm.nih.gov/21597473/#&gid=article-figures&pid=figure-2-uid-1

Referencer:

1) Philipp Schreiner, Thomas Harrer, Carmen Scheibenbogen, Stephanie Lamer, Andreas Schlosser, Robert K. Naviaux and Bhupesh K. Prusty
Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Immunohorizons. 2020 Apr 23;4(4):201-215.
DOI: 10.4049/immunohorizons.2000006

PMID: 32327453 

2) Nuno Sepúlveda, Jorge Carneiro,  Eliana Lacerda, Luis Nacul Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a Hyper-Regulated Immune System Driven by an Interplay Between Regulatory T Cells and Chronic Human Herpesvirus Infections
Front Immunol 2019 Nov 21;10:2684. doi: 10.3389/fimmu.2019.02684. eCollection 2019.
https://www.frontiersin.org/articles/10.3389/fimmu.2019.02684/full