Cortexa Weekly— February 12 2026
Research Update – Phase 1b & Phase 2 Underway
Advancing Target Validation and Strengthening the Mechanistic Foundation. We are pleased to share that Phase 1b and Phase 2 of our six phase validation roadmap are currently underway with our CRO partner in Scotland. These phases represent a critical step forward in validating our biological target and strengthening the mechanistic foundation behind our proprietary approach. Both phases are expected to conclude early next month, and we are eagerly awaiting results.
Phase 1b: RNA Sequencing Upgrade
During Phase 1a, we encountered unexpected degradation of housekeeping genes used for qPCR normalization. Rather than forcing unreliable data forward, we made the decision to upgrade the methodology.
Phase 1b now utilizes RNA sequencing to:
Eliminate dependency on unstable housekeeping genes
Provide unbiased transcriptomic profiling
Quantify receptor subunit expression
Evaluate editing and regulatory pathways
Increase statistical robustness and publishability
This shift significantly strengthens the scientific integrity of our dataset and enhances the credibility of our validation work.
Phase 2: Quantifying Receptor Proteins and Building Ratios
While RNA expression provides insight, protein quantification defines functional biology.
Phase 2 focuses on:
Quantification of receptor protein levels
Measuring subunit composition
Establishing ratios between calcium-permeable and calcium-impermeable receptor populations (AMPA v. NMDA)
These ratios are essential.
They allow us to move from conceptual narrative to quantifiable mechanistic imbalance, forming the backbone of our scientific story for:
Fundraising discussions
Strategic partnerships
Scientific publication
IND enabling positioning
If receptor imbalance can be quantified, it can be rationally targeted.
Research Spotlight
Sex Biology in Amyotrophic Lateral Sclerosis
We also want to highlight emerging research examining the role of sex biology and gonadal hormones in ALS and neurodegenerative disease progression.
Zamani, A., Thomas, E., and Wright, D.K. (2024).
Sex biology in amyotrophic lateral sclerosis.
Ageing Research Reviews.
DOI: https://doi.org/10.1016/j.arr.2024.102228
Full article: https://www.sciencedirect.com/science/article/pii/S1568163724000461
This review summarizes evidence that:
Sex differences influence ALS incidence, progression, and pathology
Gonadal hormones such as estrogen and testosterone contribute to disease heterogeneity
Hormonal signaling intersects with neuroinflammation, oxidative stress, and neuronal vulnerability
Sex specific biological processes should be considered in both research design and therapeutic development
Understanding hormonal and sex specific factors expands the broader mechanistic framework of ALS and reinforces the importance of studying upstream modulators of neuronal resilience.
Why This Matters
Completion of Phases 1b and 2 will provide:
Mechanistic validation at both RNA and protein levels
A publishable dataset
Quantitative evidence to support our biological thesis
Stronger positioning for upcoming fundraising efforts
Simultaneously, incorporating insights from sex biology research strengthens our systems level understanding of disease propagation.
What’s Next
Both phases are scheduled to conclude early next month. Once data is received and analyzed, we will:
Integrate transcriptomic and protein findings
Refine our mechanistic model
Prepare materials for publication and investor outreach
Advance toward compound validation phases
The foundation is being built now.
We look forward to sharing results soon.
— Nathan
