Jerrydylan, As I understand it, in AD there are several processes going on that relate to the glutamatergic pathways, including - 1) Some degree of excitotoxicity brought on as the disease process causes cellular destruction, similar to what happens in stroke and traumatic brain injury, with a resulting disruption in the calcium ion balance (Memantine / Namenda targets this imbalance/excitotoxicity, by reducing glutamatergic activity at the NMDA receptor). And 2) - The widespread destruction of neurons reduces the overall level of neural communication in the brain generally (fewer neurons, fewer interneural connections, etc), which impairs brain functioning.
Upregulating the glutamatergic pathways with an Ampakine might theoretically be expected to worsen #1 (excitotoxicity), except for the fact that a) Ampakines are allosteric, and as such don't initiate new neural activity on their own (as an agonist would), but instead merely amplify the existing normal neural activity, and b) low impact Ampakines like CX-717 don't induce excitotoxicity at therapeutic doses. (An AMPA or NMDA direct agonist, on the other hand, would be expected to worsen the level of excitotoxicity in AD patients, and thus would probably be contraindicated). Also, an Ampakine would improve #2 above, by getting the most out of the remaining healthy neurons/neural connections.
Of course if we go a step further and use a high impact, then we would expect a much larger effect due to the upregulation of brain neurotrophins like BDNF, which are neuroprotective / neuroregenerative.
With all the pharma interest in high impacts, I think it's safe to say that no matter what ultimately becomes of Cortex as a company, the high impact approach will be fully explored by Big Pharma. One way or another, they're going to advance this technology as long and as far as it takes to see if it works. It would be that big of a breakthrough, and the scientific and financial rewards are unbelievably enormous, since the platform could apply to virtually all neurodegenerative diseases. In the end there's possibly a Nobel prize up for grabs too.
