I wasn't sure where to post this question and was hoping to get...

I wasn't sure where to post this question and was hoping to get the thoughts of the more medical / scientific minded on the forum - this thread seemed the most suitable.

I have always been really intrigued by the mouse model results for 2591 in Prader-Willi. The neurological components were very strong and continued the themes/results we saw in PMS, PHS and AMS. I know these terms are not right (it's how my mind works), it seems like the drug "Upregulates" IGF1 when it is needed (hypoactive synaptic/neural activity) and at the same time it "Downregulates" or normalises IGF1 levels when it is needed (hyperactive synaptic/neural activity). I could be wrong but I always understood Retts and Frag X to be examples of this and that's how this drug first piqued my interest, cause if it can treat both ends of the spectrum, it should logically apply to everything between.

What really struck me about the PWS study were the physiological/cellular results and the way this drug seems to work on not just neurological issues but also physical ones. I knew it would work on a physical level given what Trofinetide does for Retts sufferers like Kaitlin and her ability to move furniture and use her arm, but I always put these improvements down to neurological changes. I thought those improvements were physical abilities linked to changes in the neural pathway - ability to control hand movements etc. I never considered them to be physiological changes of a cellular nature, where the composition of your body changes. Again, that is not the right term but the physical PWS mouse model changes were not "physical" in the sense that someone has better motor control because their brain is functioning better. As per the enclosed link, NeurenaddsPraderWillisyndrometoNNZ2591pipeline.pdf (neurenpharma.com), the study showed a reduction/normalisation in obesity and abnormally high insulin with the high dose. I was always struck by this as I had assumed that this was a neurological treatment only.

The company announcement at the time said that the results were "state dependent", which more insightful posters explained means that it has no impact on healthy people and my dreams of having the keys to the next Ozempic went up in smoke and I basically did not think about the physiological (cellular) side of 2591 again, until I recently listened to two podcasts.

The first involved a discussion with a doctor who referenced IGF and its association with cancer. He did not expand much, other than to say its a complicated field and there has been some investigation but its a very complicated field and IGF treatments are...complicated. I did some initial digging and it seems like there is some credible evidence linking abnormal IGF1 levels to certain cancers, such as breast, colorectal and prostate - Study of almost 400,000 confirms that higher blood levels of IGF-1 are a risk factor for several types of cancer — Cancer Epidemiology Unit (CEU) (ox.ac.uk). It still early days and other studies have shown it does not impact other types of cancer, with one paper I came across noting that "Possible reasons for failure include the complexity of the IGF-1R/insulin receptor system and parallel growth and survival pathways, as well as a lack of patient selection markers. While IGF-1R remains a valid target for selected tumor types, identification of predictive markers and rational combinations will be critical to success in future development.

The second podcast involved a discussion about precision medicine and noted that developing effective cancer treatments is so challenging because each cancer is unique, no two cancers are the same and how there was a lot of hope at one stage around genetic testing and sequencing being able to help the development of effective treatments. It made me think of 2591 and how it impacts a range of neurological symptoms despite different underlying genetic causes/mutations, even if it is not a genetic treatment.

I did not immediately connect the dots, and I might be connecting dots that actually don't connect but I did start thinking about whether 2591 has any applicability as a cancer treatment.

Much like the unique nature of cancers, many of the patients that 2591 will help, suffer from different/unique manifestations of their specific condition - some have less/more cognitive impairments, while others have less/more physical impairments - and the ability up/down regulate the body may in fact be an area of untapped treatment potential. As per the bolded statement above, the challenge seems to be the identification of the combination of predictive markers and with 2591, this challenge may not be relevant. It seems to normalise certain physiological aspects, no matter the specific issue.

I am certainly not saying 2591 is a cancer treatment or that we should try it as one but I am curious and I wondered whether any of the more medical/scientific minded in the forum have considered this before and where they landed with it.

It is often the case that a little information is "dangerous" and my dot connection is proof of that - but I am a curious person and the podcasts and 2591 PWS results got me thinking.