Questions over future of Alzheimer's research as more major human drug trials fail

Questions over future of Alzhe...
The discontinuation of more major human clinical trials again raises doubts over whether the current causal hypothesis for Alzheimer's disease is correct
The discontinuation of more major human clinical trials again raises doubts over whether the current causal hypothesis for Alzheimer's disease is correct
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The discontinuation of more major human clinical trials again raises doubts over whether the current causal hypothesis for Alzheimer's disease is correct
The discontinuation of more major human clinical trials again raises doubts over whether the current causal hypothesis for Alzheimer's disease is correct

Pharmaceutical giant Roche has announced it is discontinuing two major human clinical trials into the anti-Alzheimer's drug crenezumab. The decision by Roche to pull the plug on the trials comes after many similar treatments have also recently failed in human trials adding to the growing doubt about how to best tackle Alzheimer's disease.

Crenezumab is an experimental drug designed to bind to, and effect the removal of, amyloid-beta proteins in the brain. It is commonly believed that the aggregation of these amyloid-beta proteins, into what are called plaques, is the primary pathogenic cause of Alzheimer's disease, so the vast majority of current research is working to find ways to dissolve those toxic accumulations in the brain.

In 2015, crenezumab moved into the final stage of human clinical trials, after moderately successful prior trials proved the drugs safety, and potential. This phase 3 trial, dubbed CREAD, was set to run until 2021, however, an interim analysis of the results so far recently concluded the drug, while safe, "was unlikely to meet the primary endpoint of change from baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score."

"While the results with crenezumab are disappointing, they meaningfully contribute to our understanding of Alzheimer's disease," says Sandra Horning, Chief Medical Officer and Head of Global Product Development at Roche. "We gratefully acknowledge the participants in the CREAD trials and the efforts of everyone involved in this important programme."

One trial for crenezumab is still underway, focusing on a cohort of healthy subjects with a specific genetic mutation making them at high risk of developing familial Alzheimer's disease. Roche is also involved in two other major investigational trials into prospective Alzheimer's drugs. One, called gantenerumab, targets amyloid-beta proteins, albeit using a different mechanism of action from crenezumab. The other is called RG6100, and it targets the accumulation of tau, another toxic protein target often implicated in Alzheimer's disease pathology.

This latest announcement from Roche comes after a long string of similar human clinical trial failures into Alzheimer's disease treatments. Last year, pharma giant Merck announced the discontinuation of a phase 3 trial into a drug targeting amyloid-beta proteins due to ineffective results, while another big company, Pfizer, completely pulled out of all research into Alzheimer's early in 2018 due to constant trial failures.

Despite this dispiriting run of clinical trail failures, researchers in the field are not losing all hope. Some longstanding advocates of the amyloid-beta hypothesis are suggesting the toxic protein is still a good target for research but new approaches in how to combat its aggregations are necessary.

Other researchers are shooting off into a variety of different directions claiming the amyloid hypothesis has so continually failed that new ideas must be investigated. Everything from the herpes virus to gum disease bacteria are being floated as avenues for investigation, so while this clinical trial failure is certainly disappointing, it is by no means the end of the line for scientists working to find ways to fight back against this terrible neurodegenerative disease.

Source: Roche

A recent article in Fortune describes the work of several researchers led by a doctor named Paul Cox. They mention the failure of recent Alzheimers studies and suggest a possible alternative. The article is titled "Could This Radical New Approach to Alzheimer’s Lead to a Breakthrough?" and seems to be well researched.
My uneducated opinion is that all the plaque in the human body is the result of protein molecules that are created by bacteria in the gut. Called Microbiome, the huge population of bacteria is both beneficial and not. If we could eat something to kill the bad bacteria and increase the health of the good, we might see improvements all over the place. Anyway, that's my theory. I eat some plant products to try to do this, including Tribula and Inulin--both fibers that encourage growth in the good and death of the bad.
Vincent M Tedone MD
The protein aggregates found in all Neurodegenerative diseases [amyloid,Tau,TDP-43 and others] are cell debris caused by a bacteria infection Borrelia and co-infections. Current commercial laboratories do not have the correct antigens to detect these bacteria. Interesting all these ND are classified as autoimmune diseases b/c the immune system is activated.
Robert Schreib
Dear Sirs, What if there is an anti-Alzheimer's Disease drug line of research everyone overlooked? That is, when human beings sexually climax, their saliva glands emit an enzyme that dissolves chewing gum in your mouth. Stomach acid cannot do that! Chewing gum is a soft rubber, that, if swallowed, passes all the way through your gastrointestinal tract and out, intact. (If you don't believe this, try it and see! It turns the chewing gum into very tiny balls. Be careful not to choke on it!) Anyway, it is said that people who have lots of sex, also live a lot longer. So, what if this UNIQUE enzyme is somewhat responsible for that? So, if these drug researchers could obtain a sample of this enzyme, and analyze, and synthesize it, we might have a new drug that can dissolve the amyloid-beta protein plaques, inside the brains of Alzheimer's Disease patients. Hopefully, the same thing could dissolve ALL unwanted plaques throughout the human body, like the fatty plaques that line blood vessels, which causes hardening of the arteries and heart disease. Also, if this enzyme can be analyzed, it might be possible to synthesize a molecular analog of it, that is far more powerful, in doing this cure. And, I am throwing a spitball here now, when you put peanut butter on a HOT English muffin and eat it, that stuff apparently emits an enzyme, that makes your dental fillings fall out! Another line of possible research in this direction, perhaps. That covers it.