Cortexa Weekly—April 21
Growing Pains (and Progress)
We’re putting the final touches on our provisional patent, which we expect to file in the next day or two. This marks a key milestone in protecting the foundation of our therapeutic approach and sets the stage for future development.
Meanwhile, the ALS Research Program (ALSRP) has opened its pre-application window for DOD grants. We applied within an hour of it opening up, securing the application ID number 0001, because if you ain’t first, you’re last. We're already in touch with several congressional offices to help grease the wheels—because when you’re trying to fast-track neuroprotection, red tape shouldn’t be the bottleneck.
Oh, and one more thing: Cortexa is growing up. Fast. We’ve officially outpaced our LLC. What started as a scrappy startup running on caffeine and conviction now needs a real corporate backbone. We're moving ahead with C-Corp incorporation this week. Turns out, you can’t run a biotech forever on caffeine, conviction, and a glorified Venmo account.
What We’re Building Toward
Cortexa’s therapeutic hypothesis continues to gain traction: that excitotoxicity—not protein aggregation—is the true engine of progression in ALS and similar disorders. And that by intervening early in calcium dysregulation, we may be able to intercept this process before irreversible damage occurs.
We’re not alone in this thinking. Across neurodegenerative research, attention is shifting toward shared downstream mechanisms like calcium overload and mitochondrial failure—regardless of initial genetic or protein-based triggers. By focusing on these terminal states, we believe our therapeutic approach could apply broadly across ALS subtypes, including both sporadic and familial forms.
Research I’m Watching
Paper: "Excitotoxicity, Calcium, and Mitochondria: A Triad in Synaptic Neurodegeneration"
Journal: Translational Neurodegeneration (2021)
Link: Read it here
This review explores how sustained glutamatergic stimulation leads to intracellular calcium overload, triggering a destructive sequence of events within neurons. Elevated calcium disrupts mitochondrial membrane potential, impairs ATP production, and promotes the generation of reactive oxygen species. These changes activate proteases and caspases, accelerating cytoskeletal breakdown and neuronal death. Though traditionally associated with stroke, the same cascade is now recognized as a key contributor to progressive neurodegeneration in diseases like ALS, Alzheimer's, and Huntington’s.
My Take: This paper reinforces our core approach: calcium dysregulation is a final common pathway in neuron death. I agree with about 90% of what the authors are saying—the calcium cascade is real, and mitochondria (yes, the powerhouse of the cell) don’t lie. But I have to part ways with their emphasis on synaptic NMDARs as the main culprits. If NMDA receptors were truly the dominant driver here, memantine would’ve been a miracle drug, not just a modest speed bump. And their failure to mention CP-AMPARs? Honestly, that’s borderline criminal IMO.
Now I know almost all of you reading this probably do not understand the jargon here, but for the curious reader who’s made it this far: think of neurons like electrical grids. Calcium is the voltage. When too much voltage flows through the wrong wires for too long, things overheat and burn out. We, here at Cortexa, are not just flipping switches—we're rewiring the entire circuit to keep the lights on longer.
Quick Hits
Next Week's Deep Dive: I’ll be exploring a fascinating article that builds on this week’s calcium theme—focusing on how CP-AMPAR expression shifts in disease and why it might be the real villain lurking behind the scenes. Spoiler: it's going to ruffle a few feathers of the NMDA fanboys.
Grant Writing Continues: DOD submission prep in motion, with scientific figures and aims nearly complete. We're also—very cautiously—entertaining the idea of bringing in angel investors. Yes, it's a bit like dating in biotech: exciting, slightly nerve-wracking, and you’re never quite sure who’s going to ghost you after the first pitch deck. But as we scale, we know the right partner could help us go faster and farther.
Funding Update: Total raised now exceeds $2,800. Thank you to everyone who's donated so far.
Join the Movement
Each week, we’re building momentum—from compound design to IP to clinical planning. Your support means everything. Whether it’s donating, sharing our mission, or connecting us to others in the fight against neurodegeneration, we’re grateful you’re here.
