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Over 1000 Clinical trial in the past 10 years and no treatments - what's going on?

Hi everyone - Unfortunately, I have a very disturbing answer to that question. Almost all the money we donate to research goes to academic institutions that do research - research that results in papers being published and scientist going to conferences. Academic research is not geared toward finding treatments -I think most people don't know this.
On the other hand, Pharma companies and Biotech's are in the business of developing drugs to treat diseases like AD. So why have they failed so miserably spending literally billions of dollars with no treatments? The answer is )also) something that most people are not aware of.
Big Pharma and Biotech companies have drug discovery pipeline that are designed to identify a single gene or protein that can be used to treat the disease state or it's symptoms. This approach is a financially sound model since when they find something they own the drug and make billions of dollars. I have worked in the industry for over 25 years and have a deep understanding of how they work. All of the treatments that have made it to clinical trials for AD have focused on effecting a single gene or protein and they have failed. AD is caused by the dysfunction of multiple genes and proteins, as are many of the other diseases of aging. I would love to hear the thoughts and comments of other in the community on what I have said here - I know it's pretty stark but it is accurate.

  1. Thank you for sharing your thoughts based on your experience. I can understand your feelings based on what you wrote. What would be a good way for this situation to change? What do you think should be done? Scott Team Member

    1. Hi Scott,
      Unfortunately, the situation will not change anytime soon. In fact, internal funding for AD research (within biotech and pharma) is decreasing because of the high failure rate of candidate drugs. AD is a complex disease with many genes and proteins involved, and the solution will be complex. That being said, myself and two of my colleagues, all of which have family members with AD, have formed a private company and we are funding it on our own. Rest assured I did not post this to raise funds - we are not accepting outside funding at this point. Our approach is very different from traditional drug development - we are not looking for "magic bullets" to treat the symptoms of the disease. In fact our treatment is not a drug at all. It is a multi-component delivery system based on an exhaustive survey of research data using complex modeling, and a new approach to modify how multiple genes and proteins can be reconfigured to a pre-disease state. None of us were born with AD and our bodies actually contain the information on how to reverse the causal factors. The short answer is there is hope
      and are initial pilot data looks very promising. I will provide additional information as it becomes available.

      1. , fascinating! Thank you so much for sharing and we'll definitely be looking for further news as you progress. - Warmly, Donna (team member)

    2. I completely agree with the original poster and have been in a similar situation, working in drug discovery for over 20 years. I changed careers and got a PhD at the tender age of 43 to get into biomedical research because I felt most researchers are not open to new ideas, taking a genetics-based approach to everything and don't realize the shortcomings of their approach and how narrow their focus is. For example, mice are used in most AD research, but mice lack the Alu elements found in humans (> 1 million copies in the human genome). Alu elements are believed to be involved in 37 neurological and neurodegenerative disorders including AD. So, you would think researchers would question the basic value of using mice in their own research with all the shortcomings of mice. Also, although the human and mouse X chromosomes have many similar genes, the overall structures are different, causing differences in the higher-level epigenetics in the mouse and human Xs. Fortunately, human brain organoid techniques are improving as a potential alternative in AD research.

      I think epigenetics (control of gene expression) is of great importance in understanding AD and provides a multi-gene scenario. For years I was interested in lupus primarily and only started looking at AD about 2-3 years ago. I was amazed at the similarities. In fact, I recently published a hypothesis that can explain a possible route to AD based on ideas I had previously published on lupus. I developed the AD hypothesis based on a systems biology approach (rather than a narrow reductionist approach looking only at tau, amyloid-beta, or ApoE4) and based on autoimmune disease tautology. AD is a neurodegenerative AND autoimmune disease and AD has many aspects common to other autoimmune diseases. In fact, 25% of autoimmune patients have more than one autoimmune disease, of which AD can be one of them. Researchers become too narrowly focused on one disease and fail to gain insights from research on other diseases. The hypothesis is built around the nucleolus, a major epigenetic structure in cells. When the nucleolus is overly stressed it can expand and disrupt peri-nucleolar chromatin thereby disturbing epigenetic control including genes in the nucleolar heterochromatic shell and neighboring chromosomes such as tau on chromosome 17, presinilin-1 on chromosome 14, amyloid precursor protein on chromosome 21, and ApoE4 on chromosome 19. Chromosomes 14 and 21 are part of the nucleolar shell, chromosomes 17 and 19 are involved in DNA repair, a function of the nucleolus, and the inactive X chromosome (Xi, aka the "nucleolar satellite"😉 has important sequestered gene alleles that could be problematic if opened to expression. I should note that chromosomes 17, 19, 22 and Xi have very high concentrations of Alu elements. Expression of Alu elements can disrupt nucleolar integrity, even fragmenting nucleoli. It should also be noted that many autoantigens in lupus and other autoimmune diseases are at least transiently nucleolar components.
      The hypothesis was published over a month ago in Journal of Alzheimer's Disease (DOI: 10.3233/JAD-231184) and has only about 43 reads so far. I am hoping to get some feedback (pro or con) but haven't heard anything yet. It also has some ideas of experimental and therapeutic approaches for the ideas. I might try presenting the AD ideas at a conference, but a 10-15 minute time slot would be way too short for such a complicated "alternative" topic.
      I hope this line of discussion continues since I think there is a long way to go to get the research community out of a genetics-based mindset and open to epigenetics. Cancer research has always had a genetics mindset but recently the concept of some cancers arising from primarily epigenetic disruption rather than genetic mutations is being discussed.

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