CuraSen Therapeutics has dosed the first subject in a Phase 1 clinical trial of CuraAX, marking a significant step forward in addressing the challenges of neurogenic orthostatic hypotension (nOH) and associated cognitive impairment. The San Carlos-based biopharmaceutical company is developing this novel oral medication as a potential breakthrough treatment for patients suffering from sudden blood pressure drops upon standing.
Novel Mechanism of Action and Trial Design
CuraAX (CST-3056) operates as a selective, CNS-penetrant alpha-1A adrenoceptor (α1A-AR) agonist. The Phase 1 study encompasses approximately 56 healthy volunteers and includes an additional food effect cohort of six patients. Researchers will monitor various pharmacodynamic effects related to α1A-AR agonism to evaluate target engagement and potential therapeutic benefits.
The trial's primary objectives focus on establishing safety, tolerability, and pharmacokinetic profiles across multiple dose levels. This data will be crucial for informing dose selection in future Phase 2 studies.
Addressing Critical Unmet Needs
"Current treatments for nOH are limited given their non-selectivity and/or indirect mode of action, leading to significant side effects," explains Kathleen Sereda Glaub, CEO of CuraSen Therapeutics. She emphasizes that existing treatment regimens are demanding, while CuraAX promises to deliver "stable and durable efficacy, improved safety and dosing convenience, with a differentiated cognitive benefit."
The condition particularly affects patients with Parkinson's disease, multiple system atrophy, and pure autonomic failure, representing a significant orphan disease opportunity. Patients with nOH experience debilitating symptoms including dizziness, fainting, and cognitive impairment due to inadequate blood flow to the brain.
Alzheimer's Disease Connection and ADDF Support
The development of CuraAX has received funding from the Alzheimer's Drug Discovery Foundation (ADDF), highlighting its potential broader applications in neurodegenerative diseases. Dr. Howard Fillit, co-founder and chief science officer at the ADDF, notes that CuraAX's mechanism addresses one of the earliest neuropathological symptoms of Alzheimer's disease - adrenergic decline due to locus coeruleus loss.
"The activation of adrenergic receptors on neurons and astrocytes, and pleiotropic effects has the potential to not only improve cognition but to slow disease progression," states Dr. Fillit.
Pipeline Expansion and Future Directions
Beyond CuraAX, CuraSen is advancing its pipeline with additional candidates. The company plans to initiate a Phase 2b study of CuraCN later this year for major depressive disorder in older adults with cognitive decline. Furthermore, their development program includes investigating β2-AR agonists for various neurodegenerative conditions, including Alzheimer's disease, progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS).
