Lead Product

Influencing Metabolic and Immune Networks

Our lead product is 16-alpha bromoepiandrosterone, which we refer to as BEA. It is a water miscible synthetic steroid hormone that influences fundamental biological pathways affecting signaling cascades of the immune system.

BEA is best viewed as a hormone that restores dynamic immune homeostasis to a dysregulated immune system. The ability to orchestrate the immune network acts to correct dysregulated inflammatory signaling and restore effective immune responses.

Our Hypothesis

1. Declining steroid hormonal signaling, either due to aging or dysregulation, underlies IMMUNE SENESCENSE, NEUROINFLAMMATION AND AUTOIMMUNE DISEASES.

2. Restoring key components of the steroid metabolome will re-establish appropriate signaling and immune homeostasis.

The steroid metabolome refers to the complete set of steroid hormones and their metabolites present in a biological system (e.g., serum, urine, or tissues). It encompasses the biosynthesis, metabolism, and excretion of steroids, providing insights into endocrine function, disease states, and therapeutic responses Declining levels or dysregulation of the steroid metabolome are increasingly recognized as contributors to disease pathogenesis across multiple systems.

The steroid hormone of particular interest to us is dehydroepiandrosterone (DHEA). Declining levels of DHEA contribute to neuroinflammation through multiple interconnected mechanisms, as supported by recent research. These include:

• loss of neuroprotective effects due to diminished excitotoxicity mitigation and apoptotic activity
• Allowing unchecked neuroinflammatory signaling and failure to inhibit microglial overactivation, leading to excessive ROS and cytokine release
• Declining DHEA exacerbates cortisol-mediated neuroinflammation. It also impairs stress resilience, perpetuating HPA hyperactivity and inflammatory responses
• Declining DHEA also leads to synaptic and vascular function, which correlates with cognitive decline and neuroinflammatory markers
• DHEA helps maintain BBB function; its decline may increase permeability, allowing peripheral immune cell infiltration

Experience

The profile for 16-alpha bromoepiandrosterone has been assessed in in-vitro, animal and human studies. An earlier formulation completed pre-clinical and Phase I/II trials (>200 patients treated for up to 12 months) for other indications. It was during this work that an intriguing range of pharmacodynamic effects were observed, suggesting that there could be a role for conditions characterized by neuroinflammation.

While it can significantly reduce inflammation, it is not a corticosteroid and does not elicit the hyper-cortisol/Cushingoid metabolic complications of corticosteroids.

The following characteristics have been documented:

• Significant anti-inflammatory effects when tested in mouse models of asthma, the DSS model of inflammatory bowel disease and sterile inflammation of the pleura and lungs.
• Anti-inflammatory effects (↓IL-1b, IL-6 and TNF-a) in humans were demonstrated by lowering pro-inflammatory transcripts in HIV/AIDS patients. Inflammaging is one of the defining characteristics of AD.
• Data from its effects on the proliferation and function of innate immune cells suggest that it would be beneficial for immune senescent inflammation and age-related, chronic inflammatory and neuroinflammatory diseases. Treatment has been associated with significant increases in cell populations such as dendritic cells, TNK and CIK cells, CD4+ and CD8+ cells, CD123+ and CD11c+ cells. Immunosenescence is another defining characteristic of AD.
• Another mechanism of action is toggling the enzyme 11-HSD1 in key immune and somatic cells to shift the balance away from the peripheral production of active cortisol. Alzheimer brains have elevated cortisol levels which have negative effects on cognition.
• Since BEA stimulates innate immunity, it may address potential infectious causes of AD from opportunistic pathogens that arise due to immunosenescence. In a mouse model, infection with M. tuberculosis produces neuroinflammation and neurologic symptoms that mimic AD. Mice treated with BEA showed significantly better differences in short- and long-term memory, anxiety and depression.

Conclusion

DHEA deficiency fosters neuroinflammation by disrupting neuroprotection, immune balance, and stress resilience, positioning it as a critical factor in age-related and inflammatory neurological disorders. BEA is structurally related to DHEA and has been shown to be approximately 60 times more active than DHEA in tissue models.