Pipeline
Catestatin (CST)
Catestatin (CST) is a naturally occurring, 21-amino-acid bioactive peptide derived from the neuroendocrine secretory protein chromogranin A (CgA). Originally discovered as an endogenous inhibitor of nicotinic cholinergic-stimulated catecholamine release, CST has subsequently emerged as a multifunctional regulatory peptide with important actions in cardiovascular, metabolic, immune, gastrointestinal, and nervous-system physiology.
From Endogenous Peptide to Therapeutic Candidate
CST functions as an endogenous counter-regulatory peptide that helps maintain physiological homeostasis. Preclinical studies from our laboratory and collaborators have demonstrated that CST can lower elevated blood pressure, modulate adrenergic activity, reduce inflammation, improve insulin sensitivity and glucose metabolism, enhance lipid disposal, and protect cardiovascular function.
Studies in experimental models of obesity and diabetes further indicate that CST improves glucose tolerance and insulin sensitivity, promotes lipid utilization, reduces hepatic lipid accumulation, and suppresses chronic inflammation. These findings provided the foundation for our development of CST as a potential peptide therapeutic for cardiometabolic disorders.
Gastroparesis and Gastrointestinal Dysfunction
Our research has expanded CST development into gastrointestinal motility disorders. Preclinical studies indicate that CST and optimized CST derivatives can improve impaired gastric function, providing the basis for development of a new therapeutic approach to gastroparesis.
This program has now received NIH/NIDDK Small Business Innovation Research (SBIR) Phase I funding (1R43DK148298-01), "Peptide and Peptidomimetic Therapy for Gastroparesis." The project is advancing CST and next-generation peptidomimetics through preclinical efficacy, pharmacology, and therapeutic-development studies.
Neurodegeneration and Alzheimer's Disease
More recently, our research has identified an unexpected role for the CgA-CST pathway in neurodegenerative disease. Preclinical studies indicate that CST can act on multiple processes implicated in Alzheimer's disease and related tauopathies.
In experimental models, CST treatment reduces abnormal Tau phosphorylation and aggregation, suppresses neuroinflammation, modulates pathological adrenergic signaling, and improves cognitive and motor function. CST has also demonstrated activity against amyloid pathology in preclinical Alzheimer's disease models.
These findings support development of CST as a potential multi-pathway therapeutic strategy for Alzheimer's disease and related neurodegenerative disorders rather than an approach directed toward a single pathological protein.
Next-Generation CST Therapeutics
Because native peptides can have relatively short circulating half-lives, CgA Therapeuticals is developing next-generation CST analogs and peptidomimetics designed to improve stability, pharmacokinetics, dosing frequency, and therapeutic activity.
A lead next-generation candidate is retro-inverso catestatin (RI-CST), which incorporates reversed peptide sequence and D-amino-acid stereochemistry. Preclinical pharmacokinetic studies demonstrate substantially prolonged systemic exposure compared with native CST while retaining biological activity.
Our broader development pipeline includes native CST, naturally occurring human CST variants, D-amino-acid derivatives, RI-CST, and additional peptide and peptidomimetic candidates. Lead compounds are being evaluated through dose-response, pharmacokinetic, safety, ADME, efficacy, and formulation studies to identify candidates suitable for further therapeutic development.
A Multi-Disease Therapeutic Platform
CgA Therapeuticals is developing the CST platform across several areas of unmet medical need, with current programs focused on:
- Gastroparesis and gastrointestinal dysmotility
- Diabetes, obesity, and metabolic dysfunction
- Hypertension and cardiovascular disease
- Alzheimer's disease and related tauopathies
- Inflammatory and age-associated disorders
Our goal is to translate the body's own CgA-CST regulatory system into a new class of peptide and peptidomimetic therapeutics capable of restoring physiological homeostasis across multiple disease processes.
CST and its next-generation analogs remain investigational and have not been approved by the U.S. Food and Drug Administration for treatment of these conditions.