Again, wow, thank you for the feedback.
I think #120 is a bit confusing because I seeded the prompt (which becomes the title of the post eventually) with ginger gdevs and the analysis section says it is plausible but not confirmed.
The evidence focuses more on (ginsing)-GEVS and S-GEVs.
I noticed a search query keeps pinging in my Google console for “TMEM106B”. So, I asked Google what is tmem106b and whats it have to do with ALS, if anything?
Long story short, I gave my prompt suggestion and asked for a scientifically worded one, refined it a few times and came up with:
“Hypothesis: Intranasal delivery of Spermidine-modified Ginseng Extracellular Vesicles (S-GEVs) loaded with GRN mRNA exploits the cribriform plate anatomy to bypass the blood-brain barrier, providing a neuro-targeted delivery system for progranulin gene therapy that acts synergistically with spermidine-induced autophagy to suppress pathological TMEM106B amyloid accumulation and restore endolysosomal homeostasis.”
The result came back non-veridical a few times due to AI actually failing to obey and enforcer flagged it due to AI conflating evidence to suit the prompt.
Finally, I did a single run with 50x verbatim quote grounding (PathMap requires the QUOTES support the claims and the quotes are first char-by-char matched for accuracy against the stated pubmed ID) and got a response that is “hallucination free” (I am not a biologist or medical person so I cannot guarantee anything, but the software uses real API and quotes and passed the 3x hallucination checks at end).
The dataset page is #124 - Hypothesis: Intranasal delivery of Spermidine-modified Ginseng Extracellular Vesicles (S-GEVs) loaded with GRN mRNA expl
Search AI accepted the work as being valid and it made a big fuss about the Swansons Discovery:
Swansons Literature Based Discovery Candidates 124
Spermidine-induced autophagy regulation via TFEB-dependent pathways may directly facilitate the degradation of TMEM106B amylofilaments in lysosomal storage disorders.
Spermidine and autophagy in aging and neurodegeneration (e.g., PMID: 42012729PMID: 42541426)
TMEM106B protein aggregation and amylofilaments in neurodegenerative disease (e.g., PMID: 37563705)
TFEB (Transcription Factor EB), which regulates both lysosomal biogenesis and autophagic flux, activated by spermidine and impaired in TMEM106B/progranulin models.
Spermidine is a known inducer of autophagy through EP300 inhibition and TFEB activation. Since TMEM106B amylofilaments induce lysosomal dysfunction, TFEB-driven restoration of lysosomal capacity would logically prevent the accumulation of these filaments.
It could be like a biochemical pathway that tackles one of the bottlenecks in modern neurology: TMEM106B amyloid aggregation.
I am in a little over my head here as these genes and proteins are new to my knowledge set (I know, right!?! but I am learning the bio words like variables/puzzle pieces instead of understanding them fully, I just want to know how A->B->C and what constraints and context is required for the path to be true).
The main thing is that I am not trying to solve anything as much as using pathmap to extract what is already solved and give potential “next steps” and accelerate research. We can save a whole generation of ALS patients if we shave just like 2 years off how long it takes…