Maladapted Stress Response

from: <a href="https://www.healthrising.org/blog/2018/02/08/cortene-way-new-drug-trialed-chronic-fatigue-syndrome-mecfs-soon-pt/">The Cortene Way: New Drug to Be Trialed in Chronic Fatigue Syndrome (ME/CFS) Soon - Pt. I - Health Rising</a>

While drugs such as Rituxan and Ampligen were both targeted at aspects of the immune system, in contrast, Cortene was working with an experimental drug targeted at the stress system. They had no knowledge of ME/CFS, but following a chance encounter, engaged in an intensive theoretical exercise that sought to rethink every aspect of the disease. In particular, they tried to understand how a triggering event could cause relatively healthy individuals to develop dysfunction, often suddenly, in so many different systems (neuroendocrine, autonomic, immune, metabolic, thyroid, reproductive, etc.).

Cortene’s theoretical exercise made two important observations: First, that stress modulates all the systems impacted in ME/CFS; and second, that the stress response has an adaptive mechanism, which could conceivably allow the stress response system to “go off the rails” and chronically over-respond to minor stimuli.
These two observations led to Cortene’s hypothesis that ME/CFS results from a maladapted stress response in which the up-regulation of a single receptor causes an exaggerated, multi-systemic reaction to even minor stimuli. Cortene believes that this hypothesis is able to explain all of the many anomalies of ME/CFS (including gender disparity, genetic risk, diverse triggers, sudden/gradual onset, symptom variability, etc).
This has led to the first ever trial of a new drug specifically targeted at what is proposed to be the root cause of ME/CFS.

The fact that Cortene’s drug has not been approved in humans before meant a much more complex, expensive and time-consuming process was required to get approval to proceed with the trial. The investigational new drug application (IND) – which included the scientific rationale for the drug’s use, the animal efficacy, safety and toxicology studies, the plans to manufacture and formulate the drug, and the trial protocol – runs to hundreds of pages. Then there’s the all-important patent application, which has to be filed in advance of any publication, and is essential for raising the development capital that will ultimately be required to bring the drug to market—potentially $100 million.

Thus far, Cortene’s drug, a small protein called CT38, has been shown to be safe in a Phase 1 trial in healthy human volunteers. It is intended to down-regulate the receptor within hours, hopefully reversing the maladaptation and restoring patients to a pre-ME/CFS state. That is, if Cortene’s hypothesis is correct, and its experimental drug does what it appears to do in rats, the treatment is potentially curative.

Some manufacturing issues – not uncommon with new drugs, and now resolved – delayed the start of the trial a bit, but now the show is on.