Skip to Content

Guess How This Latest Alzheimer’s Trial Came Out

Yes indeed, Merck announced last night that the first Phase III trial of their beta-secretase (BACE) inhibitor verubecestat was stopped because of futility. The monitoring committee, after looking over the data so far (the trial’s been running since 2012) concluded that there was no real chance of seeing efficacy. Merck had been enrolling patients up until early last year (edit: mixed up my dates at first!) in this trial (EPOCH), which focuses, well, focused,  on patients with mild-to-moderate Alzheimer’s. They have another one going on patients even earlier in the disease process, and that’s where any hopes left for the drug will reside. Others are still trying their own compounds, too.

Are there such hopes? You really have to wonder. The list of Alzheimer’s clinical failures is impressive, but the list of failures to clinically validate the amyloid hypothesis is even more so. Recall that this is the same Merck compound that got a lot of press back in November, when the company published results that showed that it really did seem to be affected various cleaved amyloid concentrations in both humans and primates. Even back in 2012, though, when the company announced the further clinical development whose results we see today, people were wondering if they’d have a chance in this patient population. (I’ll pause to note that back then I called a headline about an effective Alzheimer’s drug being perhaps three years away “insane”, and I’m sticking with that judgment).

Beta-secretase inhibitors have failed in the clinic. Gamma-secretase inhibitors have failed in the clinic. Anti-amyloid antibodies have failed in the clinic. Everything has failed in the clinic. You can make excuses and find reasons – wrong patients, wrong compound, wrong pharmacokinetics, wrong dose, but after a while, you wonder if perhaps there might not be something a bit off with our understanding of the disease. Remember, every time one of these therapies comes around, it builds on the failures before it. Better and better attempts are made – I mean, verubecestat seems to be a pretty good compound, from the preclinical drug discovery perspective. It’s surely the best swing anyone’s taken at beta-secretase (and there have been many). But it just flat out did not work.


And let me take a minute to congratulate the drug discovery folks there on the compound itself. The fact that it does not work in the clinic is not their fault; it’s because we don’t know what the hell we’re doing in Alzheimer’s. Once you’ve decided that “We’re going to go after beta-secretase, because it’s absolutely one of the most solid ideas in the field”, the die is cast. But getting a good inhibitor for that target has not been easy. This one goes back to the Schering-Plough organization, later taken over by Merck, who came up with some interesting BACE-binding motifs while doing fragment screening. Verubecestat’s unusual “head group” came out of this work, and it’s worth thinking about how if you drew that structure on the glass of your fume hood, you’d probably have several people stopping by to tell you that you’re a fool. (Edit: structure updated, since I left out an amide carbonyl while I was redrawing it yesterday. That analog apparently didn’t work!) They’d especially be interested in your belief that a sulfonylguanidine would be a CNS drug. It doesn’t look like your run-of-the-mill combination of functional groups, but it gets into the brain, hits its target, and was good enough to be put into a gigantic series of Phase III trials. No, the people who came up with this deserve a lot of credit – mind you, I know for a fact that a good number of people who are on those papers have since been laid off by Merck, which tells you something about our industry, too.

So no, I’m not expecting much out of the prodromal Alzheimer’s patient trial that the compound is in. I will be very happy to be wrong about that, but by now, I think we have to assume that the focus on amyloid as the cause of Alzheimer’s, or even just as a method of treatment for it, is in very serious doubt.

62 comments on “Guess How This Latest Alzheimer’s Trial Came Out”

  1. Eric says:

    It is hard to have much confidence that the prodromal study will work, but to date no one has completed a study in early stage patients. Lilly has argued (post-hoc!) that their previous failures occurred because the disease had progressed too far. The argument is that once the plaques set in, the damage is already initiated. If that’s true, there is still hope for BACE inhibitors. Unfortunately the only way to know is to finish another long, expensive trial.

    Incidentally, Merck stopped enrollment in EPOCH about 15 months ago, which doesn’t seem recent to me.

  2. Dr. Manhattan says:

    Not my field, but as Derek has observed, it may be time to rethink the entire amyloid hypothesis. Some very interesting work on another new direction is emerging from Beth Steven’s lab on inappropriate synapse pruning by microglial cells as a possible AD pathogenesis mechanism.

    1. Anonymous says:

      Correctly or not, Dennis Selkoe (Harvard) gets a lot of credit for originating the amyloid hypothesis. Coming from such a highly influential “thought leader,” I think it hampered the efforts (and careers) of anyone questioning the hypothesis or trying to get funding to examine alternative theories. Although the amyloid hypothesis is not yet validated by a successful therapy but not fully disproved, it’s good to see that some alternative approaches (Stevens lab, noted below) are getting a chance.

      Of course, this isn’t the first or only time that “thought leaders” didn’t quite deliver what they promised.

      1. Always Relevant says:

        “Science advances one funeral at a time” – Max Planck

      2. skeptic says:

        I don’t think it’s fair to lay too much blame (or credit) at Selkoe’s feet. As I understand it, the evidence implicating beta-amyloid in Alzheimer’s disease is unusually strong. After all, amyloid deposits are a hallmark of the disease. Mutations in the amyloid precursor protein gene and presenilins (at least some of which increase production of the amyloidogenic fragment) predispose to the disease.

        That is much better evidence than we have for lots of chronic diseases that lack a good animal model.

  3. Lane Simonian says:

    Success is type of failure and failure is no success at all (a paraphrase of a Bob Dylan quote).

    Most of what I was going to say has already been better said by Derek. I only want to add why the amyloid hypothesis has failed and what is the alternative.

    One of the critical findings about Alzheimer’s disease in the past year is the following:

    “Malinow’s team found that when mice are missing the PKC alpha gene, neurons functioned normally, even when amyloid beta was present. Then, when they restored PKC alpha, amyloid beta once again impaired neuronal function. In other words, amyloid beta doesn’t inhibit brain function unless PKC alpha is active.”

    Protein kinase C activation is the pathway to oxidative stress that triggers Alzheimer’s disease and propels its early progression. Protein kinase C activity declines as Alzheimer’s progresses due to damage to upstream receptors (especially g protein-coupled receptors).

    Two critical points. Amyloid is only one source of oxidative stress. Other sources of oxidative stress include several environmental toxins (mercury, various air pollutants, pesticides, and industrial solvents, for instance), an unhealthy diet (a diet high in sugar, carbohydrates, high fructose corn syrup, and salt), psychological stress, and chronic smoking. So if you remove various forms of amyloid you are only removing one source of that stress. That is true even for genetic mutations that increase amyloid formation. For instance, the same gene mutation (a presenilin 1 gene mutation) led to the onset of Alzheimer’s disease eight years earlier among family members in Colombia than it did in Japan. The family members in Colombia live in one of the worst mercury-contaminated regions in the world. In regards to the larger picture, remove amyloid and you only delay the onset of Alzheimer’s disease and slow down it early progression.

    Second amyloid does no damage when oxidative stress is prevented.

    “…peroxynitrite formation in cerebral blood vessels is needed for the cerebrovascular effects of Abeta…These effects of Abeta were abolished by ROS scavengers (tempol, MnTBAP), NADPH oxidase inhibition (gp91ds-tat), NOS inhibition (L-NNA) and by the peroxynitrite decomposition catalyst FeTPPS or PARP inhibition. Thus, Abeta leads to endothelial DNA damage and PARP activation via oxidative–nitrosative stress.”

    “C-terminal fragment of amyloid precursor protein induces astrocytosis.
    Furthermore, conditioned media derived from CT105-treated astrocytes enhanced neurotoxicity and pretreatment with NO and peroxynitrite scavengers attenuated its toxicity.”

    “A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Abeta(25-35).”

    Rosmarinic acid will work in mice with “halfzmeirs” but not in humans because mice generally have only two sources of oxidative stress (amyloid and psychological stress). More powerful antioxidants such as eugenol in essential oils via aromatherapy have led to improvements in cognition related to personal orientation and ferulic acid, syringic acid, vanillic acid, p-coumaric acid, and maltol in heat processed ginseng have led to improvements in behavior and cognition in individuals with moderately severe Alzheimer’s disease.

    So yes, if amyloid is your target you have to start very early and then at best you only slight slow down the progression of the disease (the results from aducanumab were skewed because about 40 percent of the participants with the Apoe4 gene taking the drug dropped out of the trial due to adverse effects, and Apoe4 carriers progress more rapidly during the early stages of Alzheimer’s disease). But the disease can be treated at any time using the right antioxidant or combination of antioxidants.

    1. Sum kid says:

      Wait, so you believe you can explain why aducanumab appears to work? Do you believe it is due to an imbalance in the number of apoe4 carriers in the drug arm vs the placebo arm of the study?

      1. Lane Simonian says:

        Some of the apparent slowing down in the progression of Alzheimer’s disease in the aducanumab trial can likely be explained by the imbalance between apoe4 carriers in the drug group and in the placebo group. It is interesting that at six months, there were only slight differences in test scores between the drug and placebo groups.

        It may be that it takes the drug more than a half year to kick in or it may be in part a refection of more apoe4 dropouts in the drug groups after six months (particularly at the highest dose).

        Removing amyloid oligomers likely does slow the progression of Alzheimer’s disease early on, but probably not as much as the initial aducanumab results seem to suggest.

  4. anon says:

    Lots to comment on perhaps later, but need to correct the verubacestat structure as drawn, missing a carbonyl oxygen (amide, not amine).

    1. Morten G says:

      Heh, that was actually the bit I found odd, not so much the sulfonylguanidine ring. I didn’t know the structure in advance so I guess my med chem intuition isn’t too bad.

    2. Nick K says:

      Structure is still not right! It’s missing a nitrogen (guanidine rather than the amidine shown).

      1. Nick K says:

        Sorry – I failed to notice that someone else had already pointed out this error.

  5. Dr CNS says:

    Derek – A minor change in the structure… need to add a carbonyl to make it a picolinamide.
    Too bad this didn’t work…

  6. Barry says:

    Clinical failures in late-stage patients without invalidating the drug target isn’t unique to Alzheimer’s. This is a routine experience in e.g. kinase inhibitors in Oncology. Even Gleevec which is so impressive in early CML (when there is only one mutation, creating the Philadelphia Chromosome) gave only transient relief in later (“Blast Crisis”) CML. But routinely, a new prospective oncology drug is only a clinical population that has already failed standard therapy, i.e. late-stage patients with many mutations.
    No one knows how many potential drugs that might have been very effective against early-stage cancer or pre-cancerous lesions have been discarded because they failed Clinical trials against such an advanced-stage clinical population.

    1. hn says:

      Is there a publication containing such a list?

      “No one knows how many potential drugs that might have been very effective against early-stage cancer or pre-cancerous lesions have been discarded because they failed Clinical trials against such an advanced-stage clinical population.”

    2. Mol Biologist says:

      Barry, I certainly don’t disagree with that. I think we are talking about same factors. “Catch it early” until the metabolism become irreversible. In case of late AD treatment by MK-8931 you may also have only short transient relief which hard to notice in large clinical trials due to uneven progression of the disease.

      But I doubt that that many “drugs” that failed for late-stages of cancer would be valuable for early-stage cancer or pre-cancerous. Gleevec has pronounced gastrointestinal effect which not always required for cancer treatment.

  7. Peter Kenny says:

    Sad to see this happen. Perhaps the ‘thought leaders’ of Drug Discovery will say that Alzheimer’s can only be conquered when we harness Bayesian Artificial Intelligence to minimize property forecast index and we accept that exponentially-damped, multi-objective, deep learning will be a genuinely disruptive technology once it’s running on half the planet’s mobile devices.

    From a design viewpoint it is worth noting that guanidine and sulfonyl are mutually electron-withdrawing in this structural context so each will tend attenuate the other’s string.

    1. Curious Wavefunction says:

      “For a successful technology, reality must take precedence over public relations, for Nature cannot be fooled.” – Richard P. Feynman (who died on this day in 1988 and whose words are more relevant than ever)

      1. Peter Kenny says:

        A most timely and apposite quote, Ash

  8. Anon says:

    The gene for BACE is often touted as being genetically validated in man, but it’s not. No mutations in the human BACE general are associated with AD. Mutations in the gene encoding APP are associated with AD, therefore, the gene itself needs to be targeted.

    1. Eric says:

      Given that everything has failed in AD clinical trials one could argue that no gene has been validated in man.

      1. bank says:

        Genome-wide studies have validated numerous genes as *contributing* to AD risk. Classical genetic studies identified APP and presenilin as causing early onset AD. Both classical and genome-wide studies have shown that the biggest risk factor is the APOE gene. There are three isoforms of APOE, and the risk for late onset AD between homozygotes with the highest risk isoform (APOE4) is more than 100-fold greater than that for homozygotes with the lowest risk form (APOE2).

        There’s not much in the way of significant pharma effort targeted at APOE, however, which always surprised me. Perhaps another reader here will weigh in on why that might be the case?

    2. Lane Simonian says:

      One line of thought is that certain genetic mutations produce forms of the amyloid precursor protein that are more easily cut by the BACE1 enzyme.

      “For example, BACE cleaves APP with the Swedish FAD-causing mutation (APPswe) ∼10- to 100-fold more efficiently than wild-type APP, as expected for β-secretase.”

      Excess amounts of the amyloid precursor protein itself can contribute to the onset of Alzheimer’s disease. It may be in certain genetic cases, removing amyloid early may stop or at least delay the onset of the disease. Certain antioxidants, however, will do the same thing probably at nearly any stage of the disease.

  9. Not Telling says:

    I did actually make the structure incorrectly drawn above and it was inactive.

  10. luysii says:

    Certainly these are the times that try the souls of those believing in the amyloid hypothesis. One fairly strong piece of evidence is the following

    2 August ’12 Nature (vol.  388 pp.  38 – 39, 96 – 99 ’12).  A mutation has been found in the amyloid precursor protein which PROTECTS against Alzheimer’s disease.  The authors sequenced the APP gene of 1,795 Icelanders, just to look for low frequency variants.  A mutation was found 1 amino acid away from the site cleaved by beta secretase (it changes amino acid #673 from alanine to threonine (written A673T).  When the protein is cleaved this becomes amino acid #2 of the Abeta peptide.

    The mutation is far from common — around 1/200 in Scandinavian populations, and even lower in the more heterogeneous North American population.

    Then they looked at two groups of people — those with and those without Alzheimer’s disease.  5 times fewer people with Alzheimer’s disease 1/1000 had the mutation than those without, so the mutation in some way is associated with protection against the disease.

    What’s going on?  A study in isolated cells shows that the mutation is associated with a 40% reduction in the formation of Abeta peptide from APP.  This makes sense. A different variant at this position (alanine to valine) INCREASES Abeta formation, and is associated with Alzheimer’s.  So this is excellent evidence that APP and Abeta are involved in Alzheimer’s disease.

    The news gets better and better, the (rare) variant increased the odds of reaching 85% by 50%.  Then they studied people over 85 living in nursing homes.  41 carriers of A673T had better cognitive function that 3,673 non carriers.

    However, it certainly is time to look for other causes, no matter how far fetched. Here are two —

  11. Lane Simonian says:

    To highlight a central point:

    The variant is rare, but it has a huge impact on those fortunate enough to inherit even a single copy of it. About 0.5% of Icelanders are carriers, as are 0.2–0.5% of Finns, Swedes and Norwegians. Compared with their countrymen who lack the mutation, Icelanders who carry it are more than five times more likely to reach 85 without being diagnosed with Alzheimer’s. They also live longer, with a 50% better chance of celebrating their 85th birthday.

    Producing less amyloid does not guarantee that someone will avoid getting Alzheimer’s disease. It only reduces the risk as do many other interventions (a Mediterranean diet, for instance). Amyloid is only one of many factors that increase the risk for Alzheimer’s disease (amyloid is both a consequence and a contributor to oxidative stress). In some genetic cases, too much amyloid or very little amyloid may magnify its importance, but to extrapolate from there to all cases of Alzheimer’s disease is where the problem of using genetic evidence to “prove” the amyloid hypothesis of Alzheimer’s disease begins.

  12. mallam says:

    Wonder why drug prices are high…..wonder,,question..wonder….

    1. Anon says:

      Drug prices have – and should have – *nothing* whatsoever to do witg the cost of development. They are high simply because people, or at least payers and providers, are willing and alble to pay such a price, at least for now. If the cost of development is high, it simply means that pharma won’t make as much profit, and may even lose money or go out of business, but pharma will always charge the highest prices it can so long as people are willing and able to pay them.

      Just look at Marathon’s 6000% price increase, which has nothing to do with its <$10M investment in "development", if you can even call it that.

      1. Hap says:

        The prices of drugs always have something to do with the costs of development – if you can’t make those costs back when you sell the drug (and can’t beat the benefits of parking the money you spent in a CD or an index fund), then no one else is going to spend the money to develop one (and the costs of future drugs when they exist will likely increase because there won’t be as much competition). The cost of development (and investment cost) plus the cost of goods sets a floor on what the price of the drug can be. If it can’t be sold for that price, or no one’s going to buy it for that price, then it isn’t going to be made, or more of them won’t be made in the future.

        On the other hand, this doesn’t mean that drug companies won’t sell their drugs for as much as they can get for them, and the price of a drug won’t necessarily depend on its research costs or its cost of goods.

        1. Anon says:

          Utter rubbish! Price is what customers are willing and able to pay – not what you *want* to set it at so that you can make a nice profit, even though nobody will buy at that price.

          Yes, ultimately Pharma does have ultimate control to set its own price, but a hypothetical value that nobody will pay is meaningless.

          Thus, covering development costs is a wish, not necessarily a reality in setting a price.

          1. Hap says:

            Except if you can’t cover development costs, you’re not going to be making drugs for long. No one else will, either, at least if they learn from your example.

            If it costs you $50/day to go to work somewhere and you only make $40/day, how long do you think you’d be working there? You could ask for $200/day or $500/day or whatever you can get, but if you don’t make $50/day, you’ll probably be doing something else.

          2. Anon says:

            @Hap, that’s the point: you can’t keep raising the price; you just go out of business.

            There is a simple concept called the “Value Stick”, based on 3 value reference points:

            1. Your cost to produce something
            2. The price you sell it at
            3. Its value to customers

            Now, the only way to make a profit is if 3 > 2 > 1:

            i) If 3 < 2 then you're screwing customers, but customers are not stupid and they won't buy for long (if at all), so you lose money and go out of business.
            ii) If 2 < 1 then you are selling at a loss, so you lose money and go out of business.
            iii) And if 3 < 1, then the entire business model is screwed regardless of price, because either i or ii above must be true, so you lose money and go out of business.

  13. Emjeff says:

    Who wants to bet that at some point, far in the future, it’s found that Alzheimer’s is an infectious disease?

    1. Anon says:

      Now that the industry is close to settings the reset button on AD drug discovery, you’ll be long since dead when they figure that out.

    2. Crocodile Chuck says:

      Ask Barry Marshall & Robin Warren.

    3. loupgarous says:

      Alzheimer’s disease has many of the hallmarks of a prion encephalopathy. In which case the amyloids could be more effect than cause. My money is more on a strong hereditary susceptibility to Alzheimer’s disease, as is the case with familial and new variant Creutzfeldt-Jakob.

      The evidence is preponderant that nvCJD is caused by ingestion of infected meat by humans who are genetically predisposed to make pathological prion-associated brain proteins; the meat passed laterally among cattle by concentration of prions in the bovine food chain through inclusion of beef and other meat by-products.

      One part of controlling Alzheimer’s might be to do what we’ve needed to all along for other reasons – impose better top-down food biosecurity. Get the slaughterhouse out of our food chain, introduce and standardize “vatted” meat protein in the human (and obligate carnivore pet) diet (the evidence for food-chain transmission of spongiform encephalopathy from bovines to other species is even more persuasive in pets fed meat by-products from British cattle than it is for bovine-human transmission through the food chain), Get meat by-products out of the dairy animal food chain, out of commercial fowl meats, consider a broad-based ban on cervid meats until cross-over of Chronic Wasting Disease from the cervid population into other large food animals and into humans can be ruled out, and

      Time to do some broad-based, wide-ranging epidemiology across the human species, to determine which subgroups have less (or even no) Alzheimer’s, and why this is the case. If production of one or more pathological forms of a protein further up in the causative chain of Alzheimer’s disease than beta-amyloids can be definitely shown to differ by genetic predisposition, that gives us our best chance of finding an effective target for drugs to treat the disease. Better epidemiology might also determine exactly what role diet plays in the pathogenesis of Alzheimer’s.

      Until we do that, pharmacology is ammunition in a gun aimed by a nearsighted chimp.

      1. NMH says:

        Here’s a fun book along these lines. Not sure if I agree with the hypothesis, but Waldmann is a great writer, and its fun to read:

          1. NMH says:

            Excellent. Thanks for the ref, I will buy it soon.

  14. Anon says:

    The best hope we have of curing, or at least avoiding Alzheimer’s Disease is and always has been *not* treating heart disease and cancer.

    1. Eric says:

      The same could be said for not vaccinating and not wearing seat belts. Let ’em die young and they won’t get Alzheimer’s. Not a great public health strategy however.

      1. diver dude says:

        It depends what your heath strategy is trying to achieve. A “not wearing seat belts” policy provides lots of organs for transplant.

        1. Anon says:

          Actually it is proven that the introduction of seatbelts just caused people to drive faster with more accidents, so that overall mortality rate stayed constant.

          1. Isidore says:

            That’s a correlation, which does not necessarily imply causality. The introduction of seat belts and their mandatory use coincided also with changes in automobile design, with smaller cars, made with inexpensive plastic materials, being able to reach high speeds.

    2. loupgarous says:

      For that matter, forget finding new antibiotics; treating people for potentially-lethal bacterial infections just leaves more people alive who’ll catch Alzheimer’s later – right? Let’s tell Detroit to stop with the seat belts and air bags, already, and institute gun giveaways in junior-high schools to really hammer on the incidence of Alzheimer’s disease. A cure is in sight!


    Keep in mind the 2 following papers by Maiken Nedergaard and colleagues:
    1. A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β. Science translational medicine 4, no. 147 (2012): 147ra111-147ra111.
    2. Sleep Drives Metabolite Clearance from the Adult Brain. Science 342, no. 6156 (2013): 373-377.
    The papers demonstrate that there is a paravascular clearance system in the brain that clears the brain of lots of undesirables, including Amyloid β, but that the system is only active during sleep.

    1. luysii says:

      Christophe: That’s exactly what I was discussing in the link in my previous comment on this post.

  16. Mol Biologist says:

    Be persuasive known to be persistent. Instead of looking for “good inhibitor” for that target. I will try to understand what was abandoned in gut microbiome and not delivered to the brain. I believe this is a complex task and one molecule can not improve the problem.

    1. DrOcto says:

      that article lost me at ‘ composition is composed’

  17. abc says:

    The ever present failure of comercial drugs–The infamous “churn and burn” of small molecules pioneered by Ben Cravatt and other chemical biologists has failed. If your spending your days in the chemical hood, your not helping human health and you are becoming dumber by the day.

  18. abc says:

    The ever present failure of comercial drugs–The infamous “churn and burn” of small molecules pioneered by Ben Cravatt and other chemical biologists has failed. If your spending your days in the chemical hood, your not helping human health and you are becoming less intelligent by the day.

  19. Morten G says:

    It seems like all these trials are conducted on old people. Are they? Wouldn’t we expect the drugs to be most effective (if they are effective) in patients with early onset familial AD? Just like statins are much more effective in patients with familial hypercholesterolemia. I would also expect the early onset population to be much closer to the mouse models and to have fewer comorbidities to obscure any signal in the data.

    But I guess that’s why the pharma CEOs are CEOs and I’m just some poor slob.

    1. Ian Malone says:

      Indeed! And people are trying that, examples include the DIAN-TU trial and I think they are trying treatments on the Colombia kindred, probably others I don’t know about. There are downsides though; there’s still controversy over how similar the dominantly inherited disease is to the sporadic form, you’ve got a more limited pool for recruitment, and if you do get a drug approved this way it would be for a relatively rare genetic condition, rather than for sporadic Alzheimer’s. It’d be a start if we did have something that worked in these people, you could then go on to try it on others with some justification, but you still have to solve the problem of who to treat and when.

      1. Morten G says:


  20. DTX says:

    Morten – Testing compounds in younger patients maybe the key. However, think about the challenge of recruiting study young participants with no signs of Alzheimer’s. If you join the study, they determine if you have early signs of Alzheimer’s.

    Does anyone want to know if they have signs of Alzheimer’s? We all forget things, but we’d like to believe it just happened, not that it’s the start of an untreatable disease like Alzheimer’s. This makes it very hard to recruit participants.

    1. loupgarous says:

      I’d have wanted to know when I was younger. I’m 59 and Hell, I’d like to know now – it’d have a strong influence on how aggressive I chose to be in treating my cancer.

  21. Paramus says:

    The lesson to be learnt here is not only that the amyloid hypothesis is flawed. But always remember, ‘thought leaders’ have thoughts, ‘opinion leaders’ have opinions and ‘Key Opinion leaders’ have key opinions! But it doesn’t mean they are correct! To often Pharma senior management take these ‘opinions’ to be gospel, after all a large sum of money was paid for the opinion, so it must be correct!

  22. anonymous says:

    The success of Keytruda emboldens Merck to pull out of other clinical studies related to AD. For now there is positive glow and who want to walk through the graveyard? Score another one for AD!

  23. DTX says:

    loupgarous – Finding out that you have early signs of cancer is crucial because most anticancer treatments are most effective at early stages of the disease. Similarly, knowing you have high blood pressure or pre-diabetes gives you the chance to modify your life style to slow or reverse the conditions.

    Alzheimer’s is different. Knowing early does little because there is no effective treatment. Changes in life style might slow it somewhat, but the impact is nothing like the benefit that weight loss & exercise gives to high blood pressure and Type II diabetic patients. These conditions also have effective drug treatments. In contrast, knowing you have early signs of Alzheimer’s would inflict a heavy mental toll.

    1. loupgarous says:

      Actually, for someone who’s got Alzheimer’s and another dread disease (say, a metastatic and moderately aggressive but treatable cancer), knowing you’ve got both allows you to make intelligent decisions about your therapy for the other disease.

      If your prognosis is only so-so for the other disease, you may choose palliative care over more aggressive therapy. Or you may not. I only got serious about managing my type II diabetes after my surgical oncologist told me it would kill me faster than my cancer would. Some of us rise to a challenge.

  24. anon says:

    still a small problem: structure is now missing an N, bonded to the SO2!!

    1. Derek Lowe says:

      Damnit, I thought there was something off with the head group when I redrew it this morning. I didn’t bother to save the original Chemdraw file, being too lazy for that, so I had to do it again. I’ll draw it fir a third time when I get home.

Leave a Reply

Your email address will not be published. Required fields are marked *

Solve the math problem. * Time limit is exhausted. Please reload CAPTCHA.