One critical receptor and its control over brain signals and bodily functions
Dysregulated serotonin signals are implicated in Parkinson’s, Alzheimer’s, dysautonomia, autoimmunity, chronic kidney disease, chronic pain, among other ACDs.
These signals are driven by upregulated CRFR2, which is reversible using agonist-mediated receptor endocytosis.
CRFR2 upregulation disrupts serotonin signals
brain
The serotonin system is organized into dedicated circuits that control numerous bodily functions (e.g. movement, memory, thermoregulation, immunity, mood, etc). Within these circuits, serotonin orchestrates other neurotransmitters to create integrated signals.
wave
CRF has a biphasic relationship with serotonin: low-level CRF acts via the CRFR1 receptor to decrease local serotonin; high-level CRF acts via upregulated CRFR2 to increase local serotonin.
To adjust a function, CRF modulates serotonin in the relevant dedicated circuit. For instance, if the body is too hot, CRF increases serotonin in the thermoregulatory circuit, to invoke a cooling response. When temperature normalizes, serotonin, CRFR1 and CRFR2 return to baseline.
crfr2
Excessive serotonin in a dedicated circuit prevents the return to baseline, leaving CRFR2 permanently upregulated.
This permits low-level CRF to increase serotonin, so dysregulating the signal and causing a specific symptom, related to the function of the circuit. For instance, CRFR2 upregulation in the thermoregulatory circuit lowers body temperature (the symptom).
crfr22
Receptors naturally up/downregulate. Our patented treatment mimics this natural process (known as agonist-mediated receptor endocytosis). It involves a single infusion of drug (CT38) that downregulates CRFR2 and restores normal serotonin signals.
the enigmatic findings of ACDs
| ACD Pathology | Fit with CRFR2-serotonin dysregulation |
|---|---|
| Different symptoms across various ACDs | CRFR2 upregulation in a particular circuit |
| Different symptoms within any given ACD | Depends on the circuits in which CRFR2 is upregulated |
| Stress-related symptom flaring | Stress triggers the CRF system |
| Symptoms worsening over time | Upregulated circuits operating at higher serotonin levels are more prone to serotonin excess and further CRF2 upregulation |
| The observed influence of early and cumulative life stress on ACD incidence | Stress triggers the CRF system |
| The sex-bias evident in ACDs | CRF system is sex-biased, via puberty-emergent changes |
| Shared symptoms across ACDs | Same dysregulating mechanism |