@LogarithmicDis @PhilAlz @pash22 @Kariem_Ezzat @dr_shibley @MemoryDoc @Jeff_Browndyke @AlbertoEspay @nvillain_alz @seb_walsh @EWidera @LTCShop @PAULJLAMONT @ProfRobHoward @MadhavThambiset @KasperKepp @RenegadeSynapse @_michael_scholl @VincentPlanche @StefanoSensi14 @Gill_Livingston @DrTFromKC @jfballenger @jasonkarlawish @JamesRuFletcher @AdamMBrickman @ManlyEpic @SFAckley @howard_gleckman @kathy_y_liu @r_merrick @nlundebjerg @NathanielChinMD @EmmyBetz @DrJoRyan @MaggieAime @OskarHansson9 @DavidJonesBrain @PTenigma @Ayisha_Sharma97 @adamhdyer @EMA_News @NICEComms @TGAgovau @CDA_AMC @MHRAgovuk @US_FDA @uni_copenhagen @_CancerRose Agree. Which is why phase 1 would not be a simple risk free exercise (as it was with simufilam). We don’t have an adequate handle on its pk/pd and anyone want to bet on its oligomerization and receptor binding? Or maybe just ask a mouse.

@PhilAlz @LogarithmicDis @pash22 @Kariem_Ezzat @dr_shibley @MemoryDoc @Jeff_Browndyke @AlbertoEspay @nvillain_alz @seb_walsh @EWidera @LTCShop @PAULJLAMONT @ProfRobHoward @MadhavThambiset @KasperKepp @RenegadeSynapse @_michael_scholl @VincentPlanche @StefanoSensi14 @Gill_Livingston @DrTFromKC @jfballenger @jasonkarlawish @JamesRuFletcher @AdamMBrickman @ManlyEpic @SFAckley @howard_gleckman @kathy_y_liu @r_merrick @nlundebjerg @NathanielChinMD @EmmyBetz @DrJoRyan @MaggieAime @OskarHansson9 @DavidJonesBrain @PTenigma @Ayisha_Sharma97 @adamhdyer @EMA_News @NICEComms @TGAgovau @CDA_AMC @MHRAgovuk @US_FDA @uni_copenhagen @_CancerRose Ah! The Goldilocks effect. This porridge is too hot, ...too cold, ...just right. There absolutely does not have to be any just right amount of Aβ42. Why conflate philosophy with empirical science?

@PhilAlz @LogarithmicDis @pash22 @Kariem_Ezzat @dr_shibley @MemoryDoc @Jeff_Browndyke @AlbertoEspay @nvillain_alz @seb_walsh @EWidera @LTCShop @PAULJLAMONT @ProfRobHoward @MadhavThambiset @KasperKepp @RenegadeSynapse @_michael_scholl @VincentPlanche @StefanoSensi14 @Gill_Livingston @DrTFromKC @jfballenger @jasonkarlawish @JamesRuFletcher @AdamMBrickman @ManlyEpic @SFAckley @howard_gleckman @kathy_y_liu @r_merrick @nlundebjerg @NathanielChinMD @EmmyBetz @DrJoRyan @MaggieAime @OskarHansson9 @DavidJonesBrain @PTenigma @Ayisha_Sharma97 @adamhdyer @EMA_News @NICEComms @TGAgovau @CDA_AMC @MHRAgovuk @US_FDA @uni_copenhagen @_CancerRose LOL. Read the paper: "This alternative loss-of-function hypothesis...can be examined by assessing the clinical and neuroimaging effects of [using] non-aggregating peptide analogs to replace soluble Aβ levels above the threshold below which neuronal toxicity may occur."

@LogarithmicDis @cpiller Resuscitated implies that it once lived. 'Simulfilam' was born dead, made to look live by its 1st Western blot. Given its one biological property is that it cld be assayed, it passed preclinical & clinical tox because it did nothing. The name itself should have been the tell.

@adamfeuerstein They still have $169 million to spend. Are you sure it's over.?

@MartinShkreli It really wasn't a wise bet as you basically bet your life that the trial was conducted fairly and without notable biases, and regardless there was about a 5% chance that it could have read out statistically significant by chance alone. Nibbles wouldn't have appreciated Haiti.

@LogarithmicDis @PhilAlz @pash22 @Kariem_Ezzat @dr_shibley @MemoryDoc @Jeff_Browndyke @AlbertoEspay @nvillain_alz @seb_walsh @EWidera @LTCShop @PAULJLAMONT @ProfRobHoward @MadhavThambiset @KasperKepp @RenegadeSynapse @_michael_scholl @VincentPlanche @StefanoSensi14 @Gill_Livingston @DrTFromKC @jfballenger @jasonkarlawish @JamesRuFletcher @AdamMBrickman @ManlyEpic @SFAckley @howard_gleckman @kathy_y_liu @r_merrick @nlundebjerg @NathanielChinMD @EmmyBetz @DrJoRyan @MaggieAime @OskarHansson9 @DavidJonesBrain @PTenigma @Ayisha_Sharma97 @adamhdyer @EMA_News @NICEComms @TGAgovau @CDA_AMC @MHRAgovuk @US_FDA @uni_copenhagen @_CancerRose Either do I but that seems to be the drumbeat: lecanemab and metformin "work" because they increase Aβ. It's a simple solution that seems to sooth some people's anxiety. And like all simple solutions it's just wrong.

@PhilAlz @LogarithmicDis @pash22 @Kariem_Ezzat @dr_shibley @MemoryDoc @Jeff_Browndyke @AlbertoEspay @nvillain_alz @seb_walsh @EWidera @LTCShop @PAULJLAMONT @ProfRobHoward @MadhavThambiset @KasperKepp @RenegadeSynapse @_michael_scholl @VincentPlanche @StefanoSensi14 @Gill_Livingston @DrTFromKC @jfballenger @jasonkarlawish @JamesRuFletcher @AdamMBrickman @ManlyEpic @SFAckley @howard_gleckman @kathy_y_liu @r_merrick @nlundebjerg @NathanielChinMD @EmmyBetz @DrJoRyan @MaggieAime @OskarHansson9 @DavidJonesBrain @PTenigma @Ayisha_Sharma97 @adamhdyer @EMA_News @NICEComms @TGAgovau @CDA_AMC @MHRAgovuk @US_FDA @uni_copenhagen @_CancerRose Am impressed with how the anti-antibodies crowd go the other way & say Aβ42. They must know what I don't yet mice do: exactly how much Aβ causes a mouse cognitive impairment, plaques, neurotoxicity, synaptic failure & inflammation? Must be a homeopathic solution hiding somewhere.

@LogarithmicDis @pash22 @Kariem_Ezzat @dr_shibley @MemoryDoc @Jeff_Browndyke @AlbertoEspay @nvillain_alz @seb_walsh @EWidera @LTCShop @PAULJLAMONT @ProfRobHoward @MadhavThambiset @KasperKepp @RenegadeSynapse @PhilAlz @_michael_scholl @VincentPlanche @StefanoSensi14 @Gill_Livingston @DrTFromKC @jfballenger @jasonkarlawish @JamesRuFletcher @AdamMBrickman @ManlyEpic @SFAckley @howard_gleckman @kathy_y_liu @r_merrick @nlundebjerg @NathanielChinMD @EmmyBetz @DrJoRyan @MaggieAime @OskarHansson9 @DavidJonesBrain @PTenigma @Ayisha_Sharma97 @adamhdyer @EMA_News @NICEComms @TGAgovau @CDA_AMC @MHRAgovuk @US_FDA @uni_copenhagen @_CancerRose Damn it! If we had to do preclinical science then we (likely) would get the answer we don't want. We'd have to suppress it or wouldn't get a chance to go FIH. We shouldn't have to do the science when we can cure people now with our patented Aβ42 infusions. Trust our correlations.

@LogarithmicDis @pash22 @Kariem_Ezzat @dr_shibley @MemoryDoc @Jeff_Browndyke @AlbertoEspay @nvillain_alz @seb_walsh @EWidera @LTCShop @PAULJLAMONT @ProfRobHoward @MadhavThambiset @KasperKepp @RenegadeSynapse @PhilAlz @_michael_scholl @VincentPlanche @StefanoSensi14 @Gill_Livingston @DrTFromKC @jfballenger @jasonkarlawish @JamesRuFletcher @AdamMBrickman @ManlyEpic @SFAckley @howard_gleckman @kathy_y_liu @r_merrick @nlundebjerg @NathanielChinMD @EmmyBetz @DrJoRyan @MaggieAime @OskarHansson9 @DavidJonesBrain @PTenigma @Ayisha_Sharma97 @adamhdyer @EMA_News @NICEComms @TGAgovau @CDA_AMC @MHRAgovuk @US_FDA @uni_copenhagen @_CancerRose Really, it's higher barely measurable Aβ42 resulting from antibodies inducing phagocytosed plaques correlate with clinical decline and a shitload of other stuff. Details, details, never let them ruin a catchy title.

@pash22 @Kariem_Ezzat @dr_shibley @LogarithmicDis @MemoryDoc @Jeff_Browndyke @AlbertoEspay @nvillain_alz @seb_walsh @EWidera @LTCShop @PAULJLAMONT @ProfRobHoward @MadhavThambiset @KasperKepp @RenegadeSynapse @PhilAlz @_michael_scholl @VincentPlanche @StefanoSensi14 @Gill_Livingston @DrTFromKC @jfballenger @jasonkarlawish @JamesRuFletcher @AdamMBrickman @ManlyEpic @SFAckley @howard_gleckman @kathy_y_liu @r_merrick @nlundebjerg @NathanielChinMD @EmmyBetz @DrJoRyan @MaggieAime @OskarHansson9 @DavidJonesBrain @PTenigma @Ayisha_Sharma97 @adamhdyer @EMA_News @NICEComms @TGAgovau @CDA_AMC @MHRAgovuk @US_FDA @uni_copenhagen @_CancerRose Amazing to see ppl so horrified when they hear 'lecanemab.' The @ucl players give only a Personal View, not a research article. They conclude "Patient-level analyses...urgently needed...and neuroimaging...to determine...clinical correlates. Exactly what you guys scream for.

@EWidera Makes me just want to take two ivermectins and call you in the morning.

@ProfRobHoward @dr_shibley @smead2 @PAULJLAMONT @pash22 @LogarithmicDis @MemoryDoc @Jeff_Browndyke @AlbertoEspay @nvillain_alz @seb_walsh @EWidera @LTCShop @MadhavThambiset @KasperKepp @RenegadeSynapse @DanielErsk1ne @PhilAlz @_michael_scholl @VincentPlanche @StefanoSensi14 @Gill_Livingston @DrTFromKC @jfballenger @jasonkarlawish @JamesRuFletcher @AdamMBrickman @ManlyEpic @SFAckley @howard_gleckman @kathy_y_liu @r_merrick @nlundebjerg @NathanielChinMD @EmmyBetz @DrJoRyan @MaggieAime @OskarHansson9 @DavidJonesBrain @PTenigma @Ayisha_Sharma97 @adamhdyer @DrewQJoseph @jocelynkaiser @jmschott @ayton_scott @Kariem_Ezzat @jesse_brodkin @MedicareGov @jnmafi Right, < £2000 per pt for testing repurposed drugs with NHS infrastructure/ salary support in short term trials. While on the other side of Queen Square your colleagues are pulling EU/US per pt rates for industry and NIH trials. Maybe go down the block to LSE and get help?

@smead2 @PAULJLAMONT @pash22 @LogarithmicDis @MemoryDoc @Jeff_Browndyke @AlbertoEspay @nvillain_alz @seb_walsh @EWidera @LTCShop @ProfRobHoward @MadhavThambiset @KasperKepp @RenegadeSynapse @DanielErsk1ne @dr_shibley @PhilAlz @_michael_scholl @VincentPlanche @StefanoSensi14 @Gill_Livingston @DrTFromKC @jfballenger @jasonkarlawish @JamesRuFletcher @AdamMBrickman @ManlyEpic @SFAckley @howard_gleckman @kathy_y_liu @r_merrick @nlundebjerg @NathanielChinMD @EmmyBetz @DrJoRyan @MaggieAime @OskarHansson9 @DavidJonesBrain @PTenigma @Ayisha_Sharma97 @adamhdyer @DrewQJoseph @jocelynkaiser @jmschott @ayton_scott @Kariem_Ezzat @jesse_brodkin @MedicareGov @jnmafi Right, soon there will be completed experience with lecanemab in presymptomatic DIAD, in preclinical sporadic AD, and with donanemab in preclinical AD.

@JamesRuFletcher @dr_shibley @smead2 @PAULJLAMONT @pash22 @LogarithmicDis @MemoryDoc @Jeff_Browndyke @AlbertoEspay @nvillain_alz @seb_walsh @EWidera @LTCShop @ProfRobHoward @MadhavThambiset @KasperKepp @RenegadeSynapse @DanielErsk1ne @PhilAlz @_michael_scholl @VincentPlanche @StefanoSensi14 @Gill_Livingston @DrTFromKC @jfballenger @jasonkarlawish @AdamMBrickman @ManlyEpic @SFAckley @howard_gleckman @kathy_y_liu @r_merrick @nlundebjerg @NathanielChinMD @EmmyBetz @DrJoRyan @MaggieAime @OskarHansson9 @DavidJonesBrain @PTenigma @Ayisha_Sharma97 @adamhdyer @DrewQJoseph @jocelynkaiser @jmschott @ayton_scott @Kariem_Ezzat @jesse_brodkin @MedicareGov @jnmafi Most of that goes to overhead (F&A), administration, regulatory, monitoring, labs, imaging, manufacturing, etc. Little is seen by the site in this case, Univ Antioquia, in direct patient care. But you all know this and are just grousing.

@ProfRobHoward @smead2 @dr_shibley @PAULJLAMONT @pash22 @LogarithmicDis @MemoryDoc @Jeff_Browndyke @AlbertoEspay @nvillain_alz @seb_walsh @EWidera @LTCShop @MadhavThambiset @KasperKepp @RenegadeSynapse @DanielErsk1ne @PhilAlz @_michael_scholl @VincentPlanche @StefanoSensi14 @Gill_Livingston @DrTFromKC @jfballenger @jasonkarlawish @JamesRuFletcher @AdamMBrickman @ManlyEpic @SFAckley @howard_gleckman @kathy_y_liu @r_merrick @nlundebjerg @NathanielChinMD @EmmyBetz @DrJoRyan @MaggieAime @OskarHansson9 @DavidJonesBrain @PTenigma @Ayisha_Sharma97 @adamhdyer @DrewQJoseph @jocelynkaiser @jmschott @ayton_scott @Kariem_Ezzat @jesse_brodkin @MedicareGov @jnmafi I listen to you. Problem is too many of the wrong people listen to you as well.

@ProfRobHoward @dr_shibley @smead2 @PAULJLAMONT @pash22 @LogarithmicDis @MemoryDoc @Jeff_Browndyke @AlbertoEspay @nvillain_alz @seb_walsh @EWidera @LTCShop @MadhavThambiset @KasperKepp @RenegadeSynapse @DanielErsk1ne @PhilAlz @_michael_scholl @VincentPlanche @StefanoSensi14 @Gill_Livingston @DrTFromKC @jfballenger @jasonkarlawish @JamesRuFletcher @AdamMBrickman @ManlyEpic @SFAckley @howard_gleckman @kathy_y_liu @r_merrick @nlundebjerg @NathanielChinMD @EmmyBetz @DrJoRyan @MaggieAime @OskarHansson9 @DavidJonesBrain @PTenigma @Ayisha_Sharma97 @adamhdyer @DrewQJoseph @jocelynkaiser @jmschott @ayton_scott @Kariem_Ezzat @jesse_brodkin @MedicareGov @jnmafi It may be outrageous $$$ but did you cost it out? Do you know what is included and not? NIA P2 small molecule trials of N<160 go out the door from $20M to +$100M, cheaper than industry. Amsterdam just finished a $31M NIA trial. Not necessarily justifying just sayin’.