Initial reflections on Cortene (CT38) drug.

My long time friend Cort Johnson has done four posts on this promising new drug for CFS/ME (and possibly other autoimmune conditions).

My own focus is the microbiome – keeping to a merging of concepts from Occam’s razor and Osler’s Principles. For a new drug that is just starting clinical trials, this presents a challenge.

The model behind this application is the HPA axis, hypothalamic-pituitary-adrenal axis. And specifically three items are cites:

  • Corticotropin-releasing factor
    • CRF1 – low stress,
    • CRF2 – high stress
  • Urocortin 1 (UCN1) – a 40 amino acid peptide that normalizes the above

What related information is on PubMed

Short Version

It appears to be established that CRF shifts are associated with issues associated with intestinal inflammation, gut permeability, and changes in the intestinal microbiota. There is a chicken-and-the-egg question. Did the microbiota change first and the others are consequences OR did things like gut permeability altered the microbiota. My working hypothesis is that the microbiota shift occurred first.

This may also explain why I seem to be able to recover from CFS/ME multiple times. My personality type has been evaluated as a Pollyanna, thus significantly less inclined to be stressed mentally, nor dwelling on the past and with a strong positive future perspective.

Bacteria links:

  • “Both CRF and UCN1 were significantly augmented by Bacteroides vulgatus and Fusobacterium varium at both the mRNA and protein levels. In particular, B. vulgatus stimulated human MoDCs, resulting in extremely high levels of CRF and UCN1. Conclusion: Stimulation of MoDCs by B. vulgatus and F. varium may be associated with CRF/UCN1-related intestinal disorders, such as irritable bowel syndrome and inflammatory bowel disease.” [2014]
  • “. In conclusion, Lactobacillus rhamnosus GG (LGG)  stimulates IL-4, IL-10 and Ucn expression ”  [2010]

How does Cortene work is the question!

My first prediction is simple: it will alter the microbiome. If it’s main mechanism of action is the microbiome, then my second prediction is that will be effective for only a percentage of patients — why? Every patient have a unique, and frequently very different, microbiome.

“Cortene’s drug, CT38, is a CRF2 agonist, i.e., it stimulates CRF2. It is comprised only of amino acids that occur naturally in the human body.” [post]

Bottom Line

This drug is still in early stages and my gut feeling is that it will have limited success for a small number of people.  The CRF/UCN imbalance is very likely real — but my bet is on a microbiome shift being the maintainer and likely cause of this imbalance.