Replies to post #39492 on RespireRx Pharmaceuticals Inc (RSPI)

[gfp927z]

Joey, >> 20 years <<


It's actually been 30 years, but if they had known about the strong respiratory effect of Ampakines earlier, it could have been a much different story.

Originally they only knew that Ampakines could boost cognition and memory (via AMPA receptors in the hippocampus area of the brain), so that was initially the thrust for Amapkine development. It's a long story and the reasons for the slow progress were many, but here's a synopsis -

Cortex's original Ampakine compounds like CX-516 were just test compounds that were too weak to be commercial drugs, and it took years to advance more potent compounds into human trials. The much stronger CX-717 was developed and showed strong efficacy in ADHD, but was derailed by a histological 'artifact' phenomenon that was seen in longer term animal toxicology studies. The regulatory climate with the FDA for cognitive enhancers had also become less favorable in general, and other companies who had been studying AMPA upmodulation ran into dosing limitation problems due to their targeting of the 'high impact' AMPA receptor (which at high doses can induce seizures).

So with Cortex's 'low impact' approach derailed by the artifact, and the 'high impact' approach having problems, it looked like the Ampakine story might be over. However, the 'artifact' was eventually shown to be merely an anomaly caused by an interaction with the fixative agent formaldehyde, but by then the company was in financial difficulties.

But luckily, independent research by Dr. Greer at the Univ of Alberta had revealed that Ampakines strongly upregulate respiratory drive in the pre-Botzinger Complex, an area of the brain that is jam packed with AMPA receptors. Cortex licensed the patent and it was off to the races again. Funding was a chronic problem, but with CX-717 they were able to show strong efficacy in Phase 2a in reversing opioid induced Respiratory Depression, and also strong efficacy in Central Sleep Apnea with the newer compound CX-1739. In these indications Ampakines clearly have significant efficacy, and as long as that's the case the company has the potential to ultimately be successful, provided there is sufficient funding to advance the clinical development program.

Then there's Dronabinol, from the merger with Pier Pharma, which also looks interesting and will be reporting Phase 2 data later his year. So in the 2nd half of 2016 we'll be seeing Phase 2 data for both CX-1739 in Respiratory Depression and also Phase 2 for Dronabinol in Sleep Apnea. So the adventure continues :o)