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/ 

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

Fibromyalgia and Food "Fix"

Years back, when I worked a desk job, I was diagnosed with Fibromyalgia.

I had been running regularly, working out, taking aerobic classes, and was very active (but not overly so). Slowly I got to the point where getting out of bed in the morning was painful. I hurt. I was miserable. Sleep was sporadic and I was slugging through the day.

Luckily, being in a management position which gave me fantastic health benefits, I was able to work with my doctor to try and figure out the cause. We did every test imaginable over a long period of time. Finally I ended up with a rheumatoid specialist who came up with Fibromyalgia.

She gave me a whole slew of prescriptions and toldl me to get on the treadmill and walk for ten minutes a day. I laughed, thinking of the races I used to run & thought she was really underestimating my abilities. I couldn't walk for five minutes.

I filled the prescriptions and took them for a few days. I really, really 1) hated the idea of taking all those pills and 2) hated the side-affects. I stopped and went back to being miserable.

However, I didn't give up. I started a search for another answer. I did NOT like the idea of being weak, spiraling into medicine dependence, or being labeled.

I ultimately went to see a nutritionist. Not your typical hospital nutritionist (here's your food pyramid, eat like it says). I went to a private doctor who believed in using food, vitamins, minerals and all that's natural to combat illnesses.

She put me on what she called a shock diet. Nothing white in my diet at all for two weeks. If it was processed with anything white I couldn't eat it. It truly was a shock. I went through withdrawals I suppose. For about three days I walked from refrigerator to pantry to almost banging into walls as I detoxed from all the junk I had been eating (I thought I was a healthy-eater!). By the time the 2 weeks were over I was comfortable with eating whole foods and rather liked the diet.

Long story, but after the shock diet, dumping all the vitamins I thought I needed and narrowing them down to a few select choices, changing my diet, etc. I have never had any of the symptoms of Fibromyalgia... It wasn't an overnight process but it was a fairly quick turnaround. (Note: when I go back to bad eating habits, don't allow myself to get sufficient sleep, I can tell when my body is heading back in the yikes direction. I adjust and get back on track.)

That was my very first real experience with looking at diet and nutrition as a "cure" rather than going with the drugs most doctors automatically prescribe. Since then I've looked for doctors who say diet, exercise, lifestyle before pulling out the prescription pad. They are hard to find.

When my cholesterol started going up my doctor (at the time) told me I just had bad genes, luck of the draw. She "allowed" me two months to try and decrease it before starting me on Lipitor. It went up. I was half-ass about working on it at the time, bought into "gene" thing.

Later I did some research, read how I could lower it naturally with diet and proper exercise. I ditched the Lipitor. My cholesterol is well below the top range and has stayed there for years. My doctor still insists on testing it more often than usual to monitor :-)

I could tell more tales...I have politely argued with many doctors, done it my way and been successful in every instance. Good research and culling through all the hype of the current fads is crucial.

I'm not saying that diet can cure everything, but we really should give it a shot first. Even if it's not "the" cure eating healthy sure will help with fighting whatever you are facing.

I now have an OK doctor. She's not "into" the same things I am but when I walk in and tell her I'm doing this or that she says OK, try it, go for it, we'll do blood tests and see how it works. She has even given me some natural alternatives when I asked. She's still a prescription pad grabber first type, but she's agreeable to trying other things.

I am getting ready to tell her I've gone totally plant based. That's going to be an interesting conversation!

One Missing Gene Leads to Fruitless Mating Rituals

RJ Note: Gotta tell you. I'm just not real sure what this all means in the scope of life. What I do know is that in my college genetics class, we had to breed fruit flies. Of course, my roommates would laugh out loud when I was trying to get the virgin flies out before they could be attacked. And then, of course, my mom wasn't overly impressed with the fruit flies who escaped and took up residence in her home. Ah, fruit flies and their abnormalities. Brings back many fond memories. In case you're wondering, I did get an "A" in the class.

Male fruit flies missing a gene for one particular odor receptor become clueless in matters of love, scientists at Duke University Medical Center have discovered.

Because they lack the ability to read important chemical cues, these flies will indiscriminately attempt to have sex with other males, and with females who have already mated. The signals they're missing are pheromones wafting from mated females and male flies. The work appears online in Nature Neuroscience.

The researchers found that the signals from this pheromone receptor are so important to the flies that the neurons are wired directly into the higher-order processing center of the fly's brain, which governs behavior. This direct connection surprised the scientists, who have studied other fruit fly courtship genes.

"It goes against the dogma that was established for the olfactory and taste systems," said Hubert Amrein, Ph.D., of the Duke Department of Molecular Genetics and Microbiology. "Our finding implies that signals from the outside don't have to go through processing stations in the chemosensory system before being connected to the higher-order brain structures."

Males without a gene called Gr32a, the gustatory receptor gene, showed normal levels of courtship with virgin females. But in competition with normal (or wild-type) male fruit flies, they were outperformed by 4 to 1. In fact, the Gr32a-lacking flies courted the male competitors in addition to the females.

To further investigate the role of the gene, researchers used decapitated, passive flies of both genders, because these do not provide any behavioral feedback that could confound the precise measurement of the sex appeal they held for the male flies being studied. Both types of males courted the decapitated virgin females equally. However, courtship attempts toward decapitated males increased only in the males lacking the Gr32a gene, and these flies attempted copulation, behavior not seen in the wild-type males.

The scientists also found that the males lacking the Gr32a gene courted females who had already mated. Wild-type males, however, were significantly less attracted by mated females, because mated females have received male pheromones during the first mating.

The hapless Gr32a-negative males tried to mate with virgin females even when they had been covered with male pheromones, behavior that the wild-type flies avoided.

"This gene was very powerful for distinguishing between genders and for determining mating status," said co-author Tetsuya Miyamoto, Ph.D., also of the Department of Molecular Genetics and Microbiology. "Male pheromone is so effective that Gr32a mutants court males with almost the same intensity as they do females."

The GR32a gene is not found in humans. "In general, the development of pheromones in human sexual behavior is not as clear-cut as one would hope," Amrein said. "We know that males and females have preferences for certain olfactory cues. The mouse has an olfactory organ, and humans have a remnant of this in the nose, but it doesn't function in people. So I think it is very difficult to make any direct connections between these gene findings in fruit flies and what happens in people."

This research was funded by NIH grants and a long-term fellowship of the International Human Frontier Science Program Organization.