Cortexa Weekly—April 30
Fiscal Sponsorship: What It Is and Why We Did It
This week, we’re announcing a major step forward in how Cortexa Therapeutics, Inc. will fund research and accelerate development: we’re in the process of partnering with a nonprofit fiscal sponsor that allows us to receive tax-deductible donations—without having to create a full nonprofit entity ourselves.
To be clear: these donations can’t be used for general business expenses or for-profit operations. Instead, every dollar will go toward our research—work that’s moving into uncharted territory with novel drug compounds and mechanisms that could reshape how ALS and other neurodegenerative diseases are treated. This isn’t just about one company’s success. It’s about creating scientific breakthroughs that benefit the entire medical and patient community.
This also means we can now access a broader range of grants and individual giving channels, while keeping our IP, strategy, and operations in-house under the C-Corp.
What We’re Building Toward
Your donations, soon-to-be tax-deductible, will directly support:
Synthesis of 4–6 analogs of our lead compound.
In vitro screening to assess potency, selectivity, and toxicity.
Potential movement into early in vivo studies if results are promising.
We’re aiming to raise $30K–$50K over the next couple of months to get these efforts underway. If successful, this work will lay the foundation for a full IND-enabling campaign (Investigational New Drug—formal preclinical data required by the FDA to begin human trials).
We’ll be launching the donation page soon, with clear instructions for how individuals and companies can contribute. Speaking of which...
How Tax-Deductible Donations Will Work
You receive a charitable tax deduction (just like donating to any other 501(c)(3)).
Your employer may match your gift—check with HR. Companies like Microsoft, Google, and others already do this.
Your funds go directly to Cortexa’s research, not salaries, overhead or marketing fluff.
We’ve chosen this route to ensure transparency, efficiency, and scalability as we grow.
Research I’m Watching
Still deep in the literature on calcium, excitotoxicity, and downstream mitochondrial failure. The more I study, the clearer it becomes: our therapeutic strategy isn’t just promising—it might be the breakthrough this field has been waiting for.
This week, I’ve been reading through a collection of studies—six in total, each about 5 to 15 pages—published by Dr. Bading and his collaborators at Heidelberg University. Their work over the past few years has zeroed in on the toxic role of TRPM4 in neurodegeneration. One of the most compelling studies is titled:
Paper: Pharmacological Targeting of the NMDAR/TRPM4 Death Signaling Complex with a TwinF Interface Inhibitor Prevents Excitotoxicity-Associated Dendritic Blebbing and Organelle Damage
Journal: Cells (2025)
Link: https://pubmed.ncbi.nlm.nih.gov/39936986/
This paper makes a compelling case that it’s not calcium alone that kills neurons—it’s calcium in the wrong place, at the wrong time, paired with a second hit: sodium influx through TRPM4 channels coupled to extrasynaptic NMDA receptors. (These are NMDA receptors located outside synapses, where they normally don't interact with TRPM4. When they do form a complex, bad things happen.) The team shows that blocking this toxic signaling complex with FP802 (a little molecule that blocks the toxic NMDAR/TRPM4 death bondage) preserves mitochondria, prevents dendritic “blebbing” (a form of neuronal swelling and distortion that signals deep distress), and protects ER-mitochondria contact sites (normally these two structures stay apart—but when mitochondria and the ER touch, they pass signals and molecules back and forth to help balance energy, calcium, and stress responses; kind of like two departments coordinating during a crisis).
My Take: This is exactly the kind of mechanism Cortexa is focused on—disrupting death signaling at its source. Their use of FP802 (a TwinF interface inhibitor) confirms what we’re betting on: that a “two-hit” model (Ca²⁺ + Na⁺) is what ultimately triggers degeneration. We’re now working to create analogs that hit a closely related pathway—not identical, but aiming at the same toxic complex and signaling cascade, but with next-gen selectivity and bioavailability.
Bonus: FP802 already showed efficacy in a mouse model of ALS. That’s not just proof-of-concept. That’s a target with traction.
Quick Hits
Fundraising partner onboarding is nearly complete. Expect donation links and grant submission support to go live in May.
SAFE note preparation underway for future fundraising beyond donations.
Thank you to the 30+ gift givers who’ve helped us raise $2,800 so far. Let’s keep pushing.
Join the Movement
We’re building Cortexa one block at a time. From molecular design to real-world deployment. Whether you’re here as a scientist, supporter, or someone affected by ALS: your presence matters.
