Cortene is a clinical-stage biopharmaceutical company targeting neuroendocrine modulation

Elucidating the neuroendocrine biology of maladaptation

Many patients with chronic disease fit the paradigm, ‘healthy until dysfunction’. We believe that this remains an under-explored aspect of medicine. We seek to understand the change precipitating the onset of dysfunction, and ideally, reverse it.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating disease, with the peculiar feature that patients often recall the day, and even the time, they became ill. Our knowledge of the corticotropin-releasing factor (CRF) system, and its adaptations to control serotonin, led us to the idea that maladaptations within this system could explain ME/CFS. We hypothesized that excessive stimulation desensitizes the restorative mechanisms in the raphe nuclei (and limbic system), leaving the CRF2 receptor up-regulated at cessation of stimulation. Such CRF2 maladaptations could occur instantaneously and would deregulate serotonin, norepinephrine and cortisol, thereby explaining the symptoms and anomalies of ME/CFS.

This hypothesis potentially applies to several other diseases, including chronic lyme disease, fibromyalgia, post-traumatic stress disorder and multiple chemical sensitivities, which overlap with ME/CFS in core symptoms, triggers, female sex bias and the involvement of the CRF system and serotonin.

We are developing CT38 to treat ME/CFS. CT38 is a potent, selective CRF2 agonist with no known off-target activity. It was shown to be safe in a Phase 1 clinical trial in healthy human subjects.

Its use as a treatment in ME/CFS is a first-in-class approach, mimicking the natural receptor internalization (or endocytosis), which normally down-regulates CRF2 when stimulation ceases.

Preliminary data from our Phase 1/2 trial in ME/CFS patients (link to site) supports both that CRF2 is up-regulated (relative to healthy human subjects), and that limited CT38 treatment resulted in symptom improvements that persisted for at least 28 days (during which symptoms were monitored), suggesting CRF2 endocytosis.