Alzheimer's drugs...more failures and a few promising trials starting...

I've posted about the failure of mainstream Alzheimer's treatments before...I think the focus on amyloid plaques is mistaken. Yes, there seems to be some good reason to address the tangles and build up in the brain at some point. However, if you're not fixing the cause of the plaque attack then it's going to happen again and be potentially worse, possibly a rebound effect?

Thus far the ONLY treatments that are working for the long-term are those that test for health issues, change diets, lifestyles, add targeted high-quality supplements to stop the root causes. Take a look at my page with recommended reading (link above) and you'll see a number of books focused on functional healing and reversal of Alzheimer's Disease and other related brain issues.

Here's a few of the latest on drugs in testing and some getting ready to start:

EXCELLENT article...
As another Alzheimer's treatment fails, experts are divided on where to next
Before I have a chance to ask dementia researcher Amy Brodtmann about the failure of yet another Alzheimer's treatment, she wants to make one thing clear.
"Whenever these drugs fail, you can't underestimate how devastating it is."
After three decades of research and billions of dollars of investment, news that another Alzheimer's drug treatment has failed means an effective treatment for the common degenerative disease is still out of reach...
https://www.abc.net.au/news/health/2020-02-26/alzheimers-drug-failure-raises-questions-about-research/11996258

My comments: At first, I thought, wow, great...although I much prefer to figure out the root causes, address those and keep it from happening...but for those looking for a magic pill the first part of the article seemed positive, as does the end...but the one sentence I pulled below shows the problems with treatments that don't address WHY...
A new treatment for Alzheimer’s
Their research has shown that, in small doses, the metal lithium is capable of reducing Alzheimer’s symptoms and could prevent the emergence of Alzheimer’s in people with a genetic predisposition to the disease. ...
...Yet the treatment cannot remedy the symptoms of Alzheimer’s once severe cognitive decline has set in; it is only effective in low doses over sustained periods before dementia symptoms appear...
http://www.mcgilltribune.com/sci-tech/a-new-treatment-for-alzheimers-250220/

ProMIS Neurosciences Initiates Natural History Study of Blood-Based Biomarkers in Alzheimer’s Disease 
TORONTO and CAMBRIDGE, Mass., Feb. 26, 2020 (GLOBE NEWSWIRE) -- ProMIS Neurosciences, Inc. (TSX: PMN) (OTCQB: ARFXF), with Toronto Memory Program, Canada’s largest and most experienced memory clinic and site for drug treatment trials in Alzheimer’s disease (AD) has initiated a pilot longitudinal study to assess the level of blood-based biomarkers in early AD with the support of Parexel, one of the world’s leading global clinical research organizations (CROs). ProMIS will leverage Parexel’s significant data management and central nervous system (CNS) expertise for the study, which it will use as the historical control arm for its anticipated Phase 1 study of PMN310, a novel antibody that selectively targets the toxic oligomeric species of amyloid beta, a root cause of AD. The dataset will help ProMIS detect a treatment signal as early as Phase 1, potentially allowing for rapid proof-of-concept at a fraction of the expense associated with traditional clinical trials. The dataset will be made available as a communal resource for Alzheimer’s researchers...
https://www.globenewswire.com/news-release/2020/02/26/1990787/0/en/ProMIS-Neurosciences-Initiates-Natural-History-Study-of-Blood-Based-Biomarkers-in-Alzheimer-s-Disease.html

UPDATE 1-Roche drug fails in early-onset Alzheimer's disease study
* Study fails in inherited form of Alzheimer’s
* Roche says 2 additional trials to continue
* 100s of Alzheimer’s drug trials have flopped (Adds details throughout, comment from Roche)
https://www.reuters.com/article/roche-alzheimers/update-1-roche-drug-fails-in-early-onset-alzheimers-disease-study-idUSL8N2AA0QG

Drugs fail to slow decline in inherited Alzheimer's disease
Two experimental drugs have failed to prevent or slow mental decline in a study of people who are virtually destined to develop Alzheimer's disease at a relatively young age because of rare gene flaws
https://abcnews.go.com/Health/wireStory/drugs-fail-slow-decline-inherited-alzheimers-disease-68881708
...The study tested solanezumab by Eli Lilly & Co., and gantenerumab by Swiss drugmaker Roche and its U.S. subsidiary, Genentech. Both drugs gave disappointing results in some earlier studies, but the doses in this one ranged up to four to five times higher and researchers had hoped that would prove more effective...

Israeli startup hopes to battle Alzheimer’s with enzyme-busting drug
After testing in lab, ProteKt Therapeutics says compound that inhibits the PKR enzyme can lead to cognitive improvements and slow the disease’s progress; road ahead is long
...Nisemblat is aware that the way ahead is long and precarious and because there is no clear, single cause of Alzheimer’s disease there is also “no single target” to aim at in trying to beat the illness.
“The traditional treatments are not beneficial,” he said. The industry has been seeking new ways to slow down the illness’s progression and halt patents’ deterioration...
https://www.timesofisrael.com/israeli-startup-hopes-to-battle-alzheimers-with-enzyme-busting-drug/ 

Updated 3/1/20 - What is working when it comes to fighting Alzheimer's Disease and other dementias?

Pretty much the only things currently having any kind of an impact long-term on the fight against Alzheimer's Disease (AD) and other forms of dementia all come from the functional side of the medical world.

That's not to say that when caught early the traditional treatments don't always fail. Sometimes, when combined with increased physical exercise, dietary changes and maybe some supplements, early intervention works and continues to work.

Sadly, most people don't talk to their doctors about failing memory until they are past the point of current traditional, mainstream medical treatments working to keep AD at bay. I have personal experience with that silence. Those close to this individual kept everyone in the dark, although to be honest we kind of noticed some signs, just didn't pick up on them as we don't see them except in short doses for holidays. The Bredesen Protocol (see other posts, plus some of my pages linked below the header) could have worked for her but they are no longer following. Long story on that one. Sad, makes me so sad, wakes me up at night thinking about what they are facing.

Anywaze...onto brighter thoughts. Oh, wait, no...the next part deals with the current status of treatments for dementias. Not good news.

Quotes from a variety of articles on the current status of "traditional" treatments (click the quote to read the entire article):

• Previous Alzheimer’s medications have targeted specific toxins that are abundantly present in diseased brains, such as the aforementioned beta amyloid. However, these drugs all failed once going into clinical trials, perhaps because they were only targeting one part of the problem.
• As drug trials fail to find an effective treatment for the most common form of dementia, could it be time to go back to the drawing board?
• Current drugs only temporarily ease symptoms and do not alter the course of the disease.
• Because there are no effective disease-modifying treatments currently available for Alzheimer’s, drugs and other approaches — such as nutritional supplements, or nutraceuticals — designed to stop or slow disease progression have become a focus of ongoing research
• On the treatment front, we still do not know what causes Alzheimer’s disease, and we do not have a cure. The drugs that have been approved slow the progression of symptoms for a period of time, but then the disease takes over again. Someone with Alzheimer’s will die of it or with it.

Great article highlighting the general things we can do to help PREVENT dementia:

https://bewell.stanford.edu/boosting-brain-health/ 

I could have posted a thousand similar quotes. Almost every article has statements of hope about future treatments...but it's almost like they're tossing a tiny bone at the readers or maybe trying to give themselves hope. If you read my blogs, the comments I post on the pages (links above), you know I think they are barking up the wrong tree by focusing on amyloid plaques.

Now for some positive news!

However, we DO have current treatments that are working and have been working. They don't involve drugs and are multi-pronged so there's no money for grants, aside from some small ones for small groups. Also, most doctors have a tendency to look down their noses at what falls under the "functional medicine" heading. Even if their patients ignore their traditional advice and drugs and opt to change their diets, lose weight, exercise, take supplements --- and improve, get better.

I'm a prime example. I had high cholesterol. I balked at taking drugs. My doctor "allowed" me 2 months, which she "graciously" extended to three for me to try and decrease it with exercise and diet. I'll admit, I didn't do much research at the time, upped my exercise routine...and failed. She scared me sufficiently into starting to take the meds. She told me it was hereditary and I just had the gene, was stuck.

A bit later I made some serious changes to my diet. I went gluten-free (before it was a "thing"), took sugar out of my diet and then eventually moved to a plant-based diet. I was vegetarian initially. My cholesterol numbers dropped, I got off the meds...and got off my acid reflux medicine (which another doc said I'd be on for the rest of my life or risk esophageal cancer...they do like to scare one!).

If you're interested in HOPE as opposed to depressing news, a feeling of doom because you have a family history of dementia or Parkinson's, have been diagnosed with MCI (mild cognitive impairment), have found you have one or two APOE4 genes or have a family member dealing with Alzheimer's Disease take a look at the APOE4.info forum --- over 3,500 people who are focused on keeping dementia at bay. There are great success stories. There are many who are discovering the site and taking control of their health daily. You can also find some excellent Facebook groups.

NOTE: Many or most of the following docs see a role for traditional drugs and treatment, they just know that it's a much bigger picture. I agree. I think there is a place for drugs and applaud our great physicians who do a great job. I just think we have a personal responsibility to do our own research, do more than just pop a pill...

Pick up or check out one or all of the following books:
Dr. Dale Bredesen - An End to Alzheimer's
David Perlmutter - Grain Brain
Steven Gundry - The Plant Paradox
Amy Myers - The Thyroid Connection
Terry Wahls - The Wahls Protocol

Or check into Zack Bush, Mark Hyman, Stephen Phinney, Jeff Volek, Valter Longo, Jason Fung, Dave Asprey, Ivor Cummings, Sachi Panda, Rhonda Patrick, Peter Attia. (No particular order of preference and you'll like some, not like others!).

Love my doctor!

I've had a lot of different doctors over the years as I've moved around. I've liked some, tolerated some, not known I could have done better earlier in my life. I finally found a doctor who is amazing.

One big reason is what she did for my parents.

I mentioned in a prior post how I searched for a doctor for them and found the doc my Dad was already seeing. He's a nice guy, liked him. However, he spent maybe 15 minutes with us on Mom's first...and although that's more than the average of 8-12 minutes per patient, it was a typical visit.

He did the basic tests, did the standard recommendation. He didn't probe. He didn't ask a lot of questions. Didn't talk about diet, lifestyle, etc. But again, that's kinda standard. Everyone is a specialist these days so they kinda act like a clearinghouse to some degree :-). Can't fault him, do like him.

Contrast that though with my doctor. Mom & Dad showed up for their first appointment and I think we spent maybe four hours with her. She asked questions. She went into great detail about what was going on with mom, tested her reflexes, checked her out physically.

I had sent her a list of tests pertaining to issues Mom was dealing with. She asked mom questions about every single item. Talked to all of us. Treated Mom like SHE was in control, something none of the other docs we've seen have done. Mom loved her. Dad liked her --- told me numerous times that she was different, gave him hope for the medical profession, first time he'd ever been impressed with a doctor. Ha.

What doctor would spend that amount of time with a patient (no extra charge)? Do every kind of test under the sun to try and identify potential issues and/or eliminate causes for various issues? All covered by insurance.
When I go to the doc the people at the front, the medical staff, all ask how Mom & Dad are doing, ditto for the doctor. When Mom goes in they all greet her, talk about God with her when she brings it up. Yep, it's a Christian based group of praying, caring people. But not in your face and not a group that prays to heal. Well, I'm sure they pray for the healing of their patients...just mean they are doctors, PAs, well-trained, do it by the book and then go the extra ten thousand miles.

If that wasn't enough there is the way she has treated me... She gives the standard suggestions re we can prescribe this or that, but when I say no she talks with me about other options. She asks about diet, exercise, sleep, etc. She listens. She will research options. She pulls up things on her computer and shows me things. 

When I first went to see her it was for blood work. I walked in, expecting the standard panel. They checked me in, then I went to get the blood taken...except in walks the doctor. She sat with me for maybe 45 minutes or longer. She asked about any health concerns I had. She asked about past issues I might have had. She and I talked about everything health-related under the sun. She found out what I wanted, liked, what I preferred re prescriptions, taking care of myself. She asked about exercise, diet, so many things. She asked knowledgeable questions about genes as it related to issues when I mentioned I'd done the health genetic testing.

She took 7 vials of blood and tested for every issue I had mentioned. She discovered minor issues that could have become major issues if she hadn't done the testing. And she gave me suggestions on how to address them in my follow-up appointment.

I send questions via their portal and danged if she doesn't answer. I've gotten where I tag her PA rather than bug her --- it's already difficult enough to get in to see her!

I'm not telling her name 'cause I don't want her overloaded :-)  She is the energizer bunny. She teaches Pilates in a side studio. She has chef's come in to teach people how to cook healthy meals. Her brother comes in once a month to do massages and he's booked out for six months I think. She hosts panels periodically on things like dealing with stress bringing in other specialists.

Love my doc. Love that she truly cares. Love that she listens. Love that she truly heard my mom, gave her so much attention. If doctors were half as good as she then we'd all be healthier and happier and not complain so much about our medical care!

Love my doc. Oh wait, I said that... Here's another: I respect my doc. I am so impressed with her work ethic, her caring --- and the fact that I don't have to introduce myself every time I go in like with most other doctors. OK, last time... LOVE MY DOC. :-)

Treating Alzheimer's Disease

Everything I've read in the mainstream is a mix of depressing currently and hopeful in the future. Generally, prevailing "wisdom" is that once you're diagnosed you're doomed. You are going to progress.

I happen to be of a mindset that there are ways to stop the progression and reverse it in many cases, but not all cases (see above for links to stories, books, doctors, etc.). However, I see case after case where even at the later stages people have calmed, have improved, using things other than current medications and/or in addition to current medications.

One story that stuck with me was about a military gentleman with diagnosed Alzheimer's Disease, was being treated via mainstream docs, who was always agitated, yelling, mad. His family started him on one of the prevailing "alternative" treatments (diet and supplements) and he calmed down, became a happy soul. It didn't change much of anything else, aside from better physical status, but he was in a better place mentally. That alone is worth the effort!

I believe that you don't stop trying, looking for the positive and working with doctors, but also using your own research and mind to build on doctor's prognosis and suggestions. In today's world of specialization, one specialized doctor may not be aware of what is going on in another aspect. Our bodies are miraculous machines that work synergistically.

Doctors are also notoriously prickly about "Google Doctors" as they call people like me. I walk a fine line and defer to their wisdom. But I still firmly believe that I have to double-check, do my own research.

(I guess that's another blog --- all my personal and friend's experiences with an incorrect diagnosis or being given a drug to treat something without ever being told how to fix it with diet or actions (ala Type 2 Diabetes and cholesterol). Personally, I use doctors to diagnose. Not that I have any problem with taking a prescribed medication if needed. We have amazing doctors, scientists, researchers and I'm blessed to live in a time where so much is available.)

When combatting cognitive issues you start early, you look at the entire body and lifestyle and then do the best you can to correct all the issues. Sadly, as I've said over and over, by the time we're willing to start addressing brain issues we're often well on the path. For some the issues start 20 years before 'symptoms" happen.

Someone close to me is a case in point. She is averse to getting help much of the time (and then sometimes she's fully on board), she has issues taking pills so supplements are difficult, if a drug has a side effect she doesn't like she flat out refuses to take it, she has so many real and imagined reasons for not moving or exercising it's extremely difficult to push, and so on.

Through it all she is still "there" most of the time. She can enjoy times with family. She knows what is going on and cries about the future. She has great days where she's going to fight this, where she will overcome and give God the glory, where she understands that using what God has provided via doctors and foods, etc., is a good thing. She knows when she is being treated like a child. She gets mad when treated like she doesn't know what's going on. Her main caretaker is great --- he involves her every step of the way.

Side note on current drug treatments for dementia: Most of the current drugs given for cognitive issues have some ugly side-effects. This individual won't take anything without reading the pamphlets. When I looked at all the drugs and saw the potential side-effects I thought "oh no, constipation..." that's all it will take...

OK, this is another blog post where I'll have to come back to it...am cooking some cauliflower, broccoli, carrots, and mushrooms so sliding over here in-between steps :-). So much on my mind after my last visit to see my parents...and every day the long list of alerts and news re: AD, cognition, dementia and health gets my little pea-brain zipping all over the place!!!

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This one is interesting.
Scientists to test drug meant to stop or slow Alzheimer’s before symptoms appear
https://www.columbian.com/news/2020/feb/08/scientists-to-test-drug-meant-to-stop-or-slow-alzheimers-before-symptoms-appear/

My thoughts? Much of the current prevailing wisdom seems to be that the amyloid plaques are protective responses. I've heard them likened to ambulances and police that swarm to a wreck. Yes, they get tangled but they are there in response not as the cause. They seem, at least from what I'm reading, to be initially protective. Then if you don't correct the underlying issue they increase, get tangled, and start causing problems.

Clearing them up after they're tangled can be beneficial. It seems that it's short-lived though if the underlying reason for them isn't addressed. Which is why most of our mainstream drugs rarely work for long. They clear them out, there is a temporary improvement or a temporary "stay" in progression, then wham things are back and often worse than before the drug. Not always given that some find or correct the problem.

Also, they've found that many people have the plaques but never develop Alzheimer's Disease or any type of dementia. Just like many people are diagnosed with Alzheimer's Disease who have other issues ranging from Lyme disease to mold toxin issues to...oh, shoot, the list is soooo long.

That's an interesting thing, too. When they first started diagnosing Alzheimer's Disease they (the wise ones of the day :-)) came up with a list of SUGGESTED criteria to consider. Somehow that became the definitive criteria. It was initially supposed to be a tool, a possibility, not a "they have it" list. Will have to see if I can find the various articles and podcasts where I heard that one...


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A few of the articles, research, and studies that caught my attention:

Is This Under-the-Radar Stock Set to Succeed in Alzheimer's Disease?
A promising new approach could potentially yield a new drug providing hope for millions of Alzheimer's patients worldwide.https://www.fool.com/investing/2020/02/07/is-this-under-the-radar-stock-set-to-succeed-in-al.aspx
In recent years, scientific evidence forged a link between P. gingivalis infection, more commonly known as gingivitis, and Alzheimer's disease. The scientific thesis for Cortexyme's approach focuses on the discovery that the P. gingivalis bacteria can enter the bloodstream and make its way to the brain, particularly in older individuals and those with a genetic predisposition. Once inside brain cells, also called neurons, the bacteria release a toxic substance called gingipains. The gingipains digest neuronal proteins leading to the death of the brain cell..

Loss of BIN1 protein in Alzheimer’s disease promotes synaptic accumulation of phosphorylated tau and disrupts tau release: Tau-directed effects of BIN1 loss in AD
https://kclpure.kcl.ac.uk/portal/en/publications/loss-of-bin1-protein-in-alzheimers-disease-promotes-synaptic-accumulation-of-phosphorylated-tau-and-disrupts-tau-release(c8017124-cc51-4c71-a39d-9f2a985aeec3).html
Polymorphisms associated with BIN1 confer the second greatest risk for developing late onset Alzheimer’s disease. The biological consequences of this genetic variation are not fully understood, however BIN1 is a binding partner for tau. Tau is normally a highly soluble cytoplasmic protein, but in Alzheimer’s disease tau is abnormally phosphorylated and accumulates at synapses to exert synaptotoxicity. The purpose of this study was to determine if alterations to BIN1 and tau in Alzheimer’s disease promote the damaging redistribution of tau to synapses, as a mechanism by which BIN1 polymorphisms may increase risk of developing Alzheimer’s disease. We show that BIN1 is lost from the cytoplasmic fraction of Alzheimer’s disease cortex, and this is accompanied by the progressive mislocalization of phosphorylated tau to synapses. We confirmed proline 216 in tau as critical for tau interaction with the BIN1-SH3 domain and show that phosphorylation of tau disrupts this binding, suggesting that tau phosphorylation in Alzheimer’s disease disrupts tau-BIN1 associations...

Alzheimer's treatments: What's on the horizon?
https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-treatments/art-20047780

PET Tracer Detects Synapse Loss Across Alzheimer’s Brain
https://www.alzforum.org/news/conference-coverage/pet-tracer-detects-synapse-loss-across-alzheimers-brain

Dementia, Parkinson's Disease and our genes...

Two articles. The first I'm posting is much better. Given that I am APOE 3/4 plus have quite a few Parkinson's genes and all kinds of other contributing nasties like short-sleep, etc. I'm primed for a potentially ugly future genetically. However, I am not gonna let those nasties be my future.

One thing I've learned over the past 8 or 9 months of bombarding my brain with all the latest and greatest research, news, podcasts, theories while trying to help my mom is that prevention is possible. The scary thing is that the nasty genes can kick in 20 years or more before you start seeing "symptoms". Often by the time you start experiencing cognitive issues you're in a battle that main-stream science currently says you will lose. There is no cure. Currently. There is great promise for changing that though, just probably not in time to help my mother. Catching it early and/or prevention is critical.

Side note: My uncle has Parkinson's and my mother, grandmother and great-grandmother all have/had some form of dementia. My other aunt has a plethora of health issues, not sure what all of them are as there's not much communication. Not aware of any Parkinson's or dementia on the paternal side of the family, tons of cancer though. And yes, I have all kinds of cancer-related bad genes...

Also, have a ton of SNPs that say I'm primed for Type 2 Diabetes. My mom was diagnosed as pre-diabetic, and told her cholesterol was too high a few years back (not sure exactly when) and they wanted to put her on meds. She changed her diet...lowered her cholesterol...blood tests currently show good on the diabetes front but she is a true sugar-holic & carb-holic (as am I)...however, she went way too far and lost way too much weight, didn't understand eating healthy vs starvation/extremely small portions! Been trying to increase her weight since last June, some success but it's a battle :-).

Anywaze, here are the two articles on Parkinson's, APOE, etc.:

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Gene ID’d as potential therapeutic target for dementia in Parkinson’s
Targeting gene linked to Alzheimer’s may reduce dementia risk in Parkinson’s
Dementia is one of the most debilitating consequences of Parkinson’s disease, a progressive neurological condition characterized by tremors, stiffness, slow movement and impaired balance. Eighty percent of people with Parkinson’s develop dementia within 20 years of the diagnosis, and patients who carry a particular variant of the gene APOE are at especially high risk.

In new research, scientists at Washington University School of Medicine in St. Louis have found a clue to the link between Parkinson’s, APOE and dementia.
https://medicine.wustl.edu/news/gene-idd-as-potential-therapeutic-target-for-dementia-in-parkinsons/

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Lab: Discovery could help stave off anguish of dementia in people battling Parkinson’s

PARKINSON’S disease can be especially cruel. Its slow but sure onset inflicts tremors, slows down movement and impairs balance. And perhaps the most bitter blow of all is that 80 percent of people newly diagnosed will go on to develop dementia within 20 years.

But there is hope for the future, after experts made a breakthrough that could lead to treatments capable of slowing down or stopping this mental decline.

https://www.metro.news/bbc-science-focus-discovery-could-help-stave-off-anguish-of-dementia-in-people-battling-parkinsons/1899963/
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Info at end of first article with study info I think:
Davis AA, Inman CE, Wargel ZM, Dube U, Freeberg BM, Galluppi A, Haines JN, Dhavale DD, Miller R, Choudhury FA, Sullivan PM, Cruchaga C, Perlmutter JS, Ulrich JD, Benitez BA, Kotzbauer PT, Holtzman DM. APOE Genotype Regulates Pathology and Disease Progression in Synucleinopathy. Science Translational Medicine. Feb. 5, 2020. DOI: 10.1126/scitranslmed.aay3069