Cortexa Weekly—April 2
Cortexa Progress
We’re moving fast. This week, we’ve been finalizing our shortlist of medicinal chemists to begin designing next-generation analogs based on our early scaffold work. (Think of this like creating improved versions of a base molecule, tailored to work better in the human body.) These efforts are focused on fine-tuning for selectivity, safety, and translational potential—laying the foundation for future preclinical studies.
We also kicked off a new round of strategy sessions with advisors to align our scientific roadmap with a clear and actionable business plan.
Still early—but every piece of this puzzle matters.
Research I’m Watching
Paper: “Hyperhomocysteinemia Increases Cortical Excitability and Aggravates Mechanical Hyperalgesia and Anxiety in a Nitroglycerine-Induced Migraine Model in Rats”
Journal: Biomolecules, May 2022
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC9138593/
This study investigates how elevated levels of homocysteine—a sulfur-containing amino acid—affect migraine-related symptoms in rats. Researchers found that increased homocysteine levels led to heightened cortical excitability, increased sensitivity to pain (hyperalgesia), and elevated anxiety levels, especially when combined with nitroglycerin, a known migraine trigger. These findings suggest that homocysteine may play a significant role in migraine pathophysiology.
My Take:
The link between homocysteine and neurological disorders continues to strengthen. This study underscores the importance of metabolic factors in conditions like migraines, which could and likely do have broader implications for neurodegenerative diseases. It adds more weight to the hypothesis I’m exploring—that elevated homocysteine may be the initial trigger that sets off the entire neurodegenerative cascade. Targeting metabolic pathways might offer new therapeutic avenues for conditions characterized by neuronal hyperexcitability.
Understanding metabolic contributors to neurological disorders can open doors to novel treatment strategies.
Quick Hits
AAV Gene Therapy Trial: A new study is recruiting early-stage ALS patients to test a gene therapy that uses a virus to tweak RNA editing. When viruses are used for good—love to see it.
Paper I’m Digging Into: A recent preclinical study suggests that cortical hyperexcitability might come before spinal motor neuron loss in ALS mouse models. BIG if true—and it fits squarely with our thinking that early excitability, not degeneration, might be what starts the fire. More to follow next week!
Biotech Moves: Companies are finally leaning into combination therapies. Momentum is building, and let’s be honest—imitation is the sincerest form of flattery.
What Drives Us
Cortexa Therapeutics is founded on one simple idea: If we can stop the first domino, we may stop the cascade.
We’re building a new class of treatments that target the earliest known disruptions in ALS—and potentially other neurodegenerative diseases. It’s early, but we’re all in.
Want to follow our journey?
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Want to help? We’re accepting donations to support our lab testing and compound development. 100% of funds go directly to R&D—no salaries, no overhead—just science.
