Tuesday, June 21, 2022
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Will There Ever Be A Cure For Alzheimer’s

How Close Are We To A Cure For Alzheimer’s

Will We Ever Cure Alzheimers Disease?

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    Answer by Sai Janani Ganesan, Postdoctoral Scholar at UCSF, on Quora:

    If you regularly read the newseither the politics or the science and technology section, you have read at least a couple of articles in the last year on Alzheimers disease or more broadly, dementia.

    AD is a neurodegenerative disease and is the leading cause of dementiaa syndrome or a condition that manifests as a group of symptoms that affect cognitive and behavioral skills due to death of neurons, arising from a multitude of largely unknown causes . There arent any medications available today that either slow or stop neuronal damage, the drugs available in the market are involved in only marginally improving symptoms and are highly patient dependent. With a total number of affected individuals predicted to increase to 13 million in the US and over 100 million worldwide by 2050, and skyrocketing costs for dementia care and expected to grow to $1 trillion by 2050), it is safe to call dementia one of the biggest public health problems of our times.

    Although first identified in 1906, it wasnt until the 70s that we began to accept AD as a leading cause of death. To quote Robert Kutzman from a 1973 Journal of the American Medical Association editorial :

    Q. Why have we not been successful or close to preventing or slowing down the disease?

    Q. Is Obamas 2025 target realistic?

    Q. How many years will it be before we see a cure for Alzheimers?

    Footnotes

    Cause Of Alzheimers Disease

    The traditional model is that Alzheimers starts when a person loses the genetic lottery and inherits a set of genes that code for misshapen brain proteins called amyloid beta and tau. During the ripe years of youth when poor life decisions only cause minimal impact and regret, these defective proteins are usually broken down by the body and hardly cause any trouble. Most people are free of symptoms up until the ages of 60 to 70. When age, stress, and hard liquor catch up , the bodys cleanup systems begin to slow down and these proteins begin building up into toxic plaques that slowly kill neurons through inflammation in the regions of the brain involved with speech, motor function, and decision-making. The process takes many decades to show up, though about 5 percent of the population is diagnosed with Early Onset Alzheimers at ages 40 to 50. Some companies are using artificial intelligence to detect Alzheimers before it hits, and even some brain interface companies are getting into the act.

    Possible Ipo In The Pipeline

    Founded in 2013, Alzheon is a clinical-stage biotech startup based out of Framingham, Massachusetts that has raised a total of $37 million after a recent venture round of $15.8 million back in 2017. Alzheons pharmaceutical technology is based on ALZ-801, a standard oral drug thats meant to dissolve amyloid beta plaques by inhibiting the formation of its precursor. After withdrawing an IPO offer of $81 million earlier this year, there has been speculation by analysts that Alzheon will continue to lose money following the failure of ALZ-801 to yield favorable results in Phase 3 trials.

    But it looks like Alzheon is pushing to refile an IPO for $40 million and will get another chance to conduct Phase 3 trials on ALZ-801. This time they plan to target a selective group of patients bearing genetic markers for a more specific subset of Alzheimers keeping their lead candidate in the game.

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    Will We Ever Cure Alzheimers Disease

    — I have a friend whose grandmother died of Alzheimers disease. I met her once when I was a child, in a little room of a large nursing home. I never forgot my friends expression — or that of her mother, who was caring for her. One in three people in the U.S. over the age of 65 will suffer from Alzheimers disease. It touches so many of us and the experience is horrible.

    At first you start to lose your memory. Then your general cognitive ability starts to drop. By the end of the disease your behavior and personality change, and you may suffer from hallucinations and seizures. From early on, you need caring for, and this is devastating for the caregivers watching someone they love have their personality stripped away from them.

    But what is happening in the brain? First, the brain tissue degenerates, starting in the hippocampus and frontal lobes, and then spreading across the whole cortex and finally into the lower brain structures. And this is what causes the changes in behavior.

    If you zoom in to the microscopic level, you can see amyloid-beta proteins coagulating between cells to form sticky plaques, and tangles of tau proteins appear within the neurons. But neither are completely responsible for the disease. And likewise, we know of many genes that contribute to making these plaques and tangles, but no gene can make you certain of contracting the disease.

    Q: Is There Anything People Can Do Now To Prevent The Disease Or At Least Delay It For Several Years

    New Alzheimers Treatment is Fully Restoring Memory Function

    In my practice, I encounter many people who have family members with Alzheimer’s and theyre worried about their genes. But in most cases, just because your mother has it doesnt mean youre going to get it.

    In a complex disease, each gene and each environmental factor is like putting a pebble on a scale. None of them by themselves can prevent or cause Alzheimers. So if your parent has Alzheimers, that puts one pebble on the scale. But if you went to college, if you exercise, those are pebbles on the other side of the scale.

    Many of the things that we thought historically cause Alzheimer’s have been debunkedfor example, the idea that it was caused by various heavy metals. But we do know that maintaining cardiac health is good: Exercise is good smoking is bad developing diabetes or obesity increases the risk. These recommendations, as most people know, are true for any disease.

    People often ask me this question, hoping I know something that no one else does. I dont have any other answers at the moment, but everyone in the field is doing their best to find new ways to forestall this disease.

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    Q: First The Bad News Why Have All Drugs Tested In The Past Several Years Failed

    In retrospect, the idea that reducing amyloid in the brainwhich all the failed drugs dois based on an incomplete picture of the disease.

    To treat a disease, we need to treat whats broken. But its very difficult to find whats broken in these slowly progressive brain disorders.

    One way to find whats broken is through genetics, but the first wave of genetic studies in the 80s and 90s only had the technical capabilities to investigate Alzheimers cases that run in families, those caused by a single gene.

    The results of these studies all seemed to converge on one biological process: amyloid.

    But these single-gene forms of Alzheimers are rareand account for maybe 2% to 3% of cases. Most cases of Alzheimers are caused by a complex interplay of many genes and the environment.

    The field made the assumption that amyloid is the primary culprit in all forms of Alzheimers. It made perfect sense, because we see amyloid in all patients with Alzheimers, whether their disease is caused by a single gene or not. The amyloid finding was extremely exciting, and there was a sense that we were on the cusp of curing this devastating, horrible disease.

    Safe And Effective In Animals

    After testing the GSM in mice, rats, and macaques, the researchers found that it significantly reduced the buildup of peptides that create plaques. Also, the drug produced no toxic side effects in any animals.

    Administering the GSM before or after the animals began to develop plaques reduced overall plaque formation. It also reduced inflammation associated with plaque buildup which is key because scientists believe that this inflammation plays a role in the diseases progression.

    The researchers hope that, eventually, the GSM might become a therapy that can inhibit the development of Alzheimers disease in humans.

    According to study co-author Prof. Rudolph Tanzi, director of the Genetics and Aging Research Unit at Massachusetts General Hospital, in Boston, In this study, we have pharmacologically characterized a potent GSM that, based on its preclinical attributes, appears to equal or exceed the potency of any previously tested GSMs. He continues:

    Future clinical trials will determine whether this promising GSM is safe in humans and could be used to effectively treat or prevent Alzheimers disease.

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    Seeking The Diseases Source

    To figure out how to treat and prevent Alzheimers disease, scientists first have to learn what causes the condition.

    Although theres a growing wealth of data on the topic, it hasnt been enough to present a single, cohesive picture.

    I think cloudy and piecemeal actually is a fairly good description of where the fields understanding of Alzheimers disease , said Dr. Keith Fargo, director of scientific programs and outreach at the Alzheimers Association, in an interview with Healthline.

    You look at HIV, and thats something where its a virus, and we know the virus that causes AIDS, explained Fargo. And so thats something very simple to link onto and research. With Alzheimers disease, thats not the case. Its probably going to be very multi-factorial.

    Much of the research is currently focusing on amyloid and tau proteins, whose malformation are classic characteristics of Alzheimers disease. But Fargo says other factors likely also play a role, including vascular health, inflammation, lifestyle, and possibly even viral causes.

    Age, Fargo says, is the number-one culprit.

    And even the two starring proteins, amyloid and tau, are laden with mystery.

    They are more likely to malfunction with increasing age, and certain genetic mutations have been linked to their deformation in a percentage of patients. But the root cause of what prompts them to begin malfunctioning in the first place remains unknown.

    A Recent Disappointment And Renewed Hope

    Is There A Cure For Alzheimer’s Disease?

    That is why so many patients, caregivers, researchers, and pharmaceutical executives groaned with disappointment in March of this year, when an especially hopeful new medication, aducanumab, was deemed a failure. Plans were made to shut down the two large trials investigating its potential after a few additional months. Aducanumab belongs to the class of drugs known as the anti-amyloid monoclonal antibodies. These molecules, manufactured biologically and injected into research subjects with early Alzheimers disease, are like magic bullets targeted at toxic amyloid similar to the way that our own antibodies attack infectious bacteria. In early trials, aducanumab appeared to have disease-modifying properties. When administered to people in an early stage of Alzheimers disease, it not only reduced brain amyloid content, it also appeared to delay cognitive decline. No wonder its apparent failure was soupsetti ng.

    Using additional data gathered during the final months of study, Biogen revised its earlier assessment. In 2020, an application for approval of aducanumab was submitted to the FDA, seeking permission to market it as an Alzheimers disease treatment. In November of 2020, a panel of experts concluded that the clinical data did not support the approval of aducanumab. The FDAs final decision is anticipated late in March of 2021.

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    The Difficulty Of Diagnosis

    Because Alzheimers disease has a wide array of causes, symptoms can vary tremendously from person to person.

    For Diane, one unexpected symptom was hallucinations. She began seeing visions of her husband and seeing images of her two daughters as young children.

    Alzheimers presents itself differently in every single person, said Chris Riley. Theres some very general things that can happen, but when people have Alzheimers, each persons experience is unique to themselves.

    This makes a clinical diagnosis, or a diagnosis off the basis of symptoms, tricky.

    The clinical diagnosis of Alzheimers disease by a physician due to his experience in the area is usually right but not always, said Dr. Victor Henderson, professor of health research and policy and of neurology and neurological sciences at Stanford University, and director of the Stanford Alzheimers Disease Research Center, in an interview with Healthline. Maybe 90 percent of the time the clinical diagnosis is accurate, a little bit less where there are atypical features.

    In 2011, the National Institute on Aging developed a report with new guidelines for diagnosis. It incorporated a wealth of new research, including a number of tests that look at biomarkers in the body to diagnose Alzheimers disease.

    For a rare few, a genetic test can reveal whether the person is likely to develop early-onset Alzheimers, a particularly swift-moving version of the disease.

    Dementia And Stem Cell Research

    Scientists have collected skin cells from people with dementia and by making them into stem cells have created brain cells in the laboratory. These can be used to provide a valuable insight into cell behaviour and the way the brain damage of dementia starts, so that potential treatments can be developed and tested.

    Alzheimers Research UK says: The findings from this work are not only applicable to genetic forms of Alzheimers but could inform our understanding of the more common non-genetic forms too. While this innovative stem cell research is not a replacement for clinical trials in people, it allows researchers to investigate key aspects of the disease in a human system.

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    Us Approves First New Alzheimer’s Drug In 20 Years

    The first new treatment for Alzheimer’s disease for nearly 20 years has been approved by regulators in the United States, paving the way for its use in the UK.

    Aducanumab targets the underlying cause of Alzheimer’s, the most common form of dementia, rather than its symptoms.

    Charities have welcomed the news of a new therapy for the condition.

    But scientists are divided over its potential impact because of uncertainty over the trial results.

    At least 100,000 people in the UK with a mild form of the disease could be suitable for the drug if it were to be approved by the UK regulator.

    The US Food and Drug Administration said there was “substantial evidence that aducanumab reduces amyloid beta plaques in the brain” and that this “is reasonably likely to predict important benefits to patients”.

    How Is Alzheimer’s Disease Treated

    Will We Ever Cure Alzheimer

    Alzheimers disease is complex, and it is therefore unlikely that any one drug or other intervention will ever successfully treat it in all people living with the disease. Still, in recent years, scientists have made tremendous progress in better understanding Alzheimers and in developing and testing new treatments, including several medications that are in late-stage clinical trials.

    Several prescription drugs are already approved by the U.S. Food and Drug Administration to help manage symptoms in people with Alzheimers disease. And, on June 7, 2021, FDA provided accelerated approval for the newest medication, aducanumab, which helps to reduce amyloid deposits in the brain and may help slow the progression of Alzheimers, although it has not yet been shown to affect clinical symptoms or outcomes, such as progression of cognitive decline or dementia.

    Most medicines work best for people in the early or middle stages of Alzheimers. However, it is important to understand that none of the medications available at this time will cure Alzheimers.

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    Q: Does That Mean The Amyloid Hypothesis Is Completely Wrong

    The amyloid hypothesis is that amyloid is the trigger of everything in Alzheimers. That seems now to be wrong.

    New studies from the past decade tell us that amyloid is part of the story of Alzheimers disease, but its the smoke, not the fire. Weve learned that the single-gene and more common, complex forms of Alzheimers are not identical, though they do overlap.

    Theres been a lot of backlash against the amyloid hypothesis lately, but in the 90s, it was the right idea. The pharmaceutical industry was right to jump on the amyloid bandwagon. And theyre now right to give it up, I think.

    Can Dementia Be Cured

    Frustratingly, medical science has so far been unable to find a cure for dementia. The truth is that there is unlikely to be a single silver bullet to treat the condition because the brain damage of dementia is caused by many different diseases. However, research is continuing aimed at reducing risk factors, slowing down the decline and improving function and quality of life.

    When someone you love is diagnosed with dementia, it can be frightening and overwhelming. Although there is no definitive remedy, doctors and researchers have a much better understanding of the condition, how it is caused and how it progresses.

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    Identifying Who’s At Risk Of Dementia

    Experts know that damage to the brain caused by Alzheimer’s disease can start many years before symptoms appear. If people at risk of Alzheimer’s could be identified at an early stage, it is hoped that treatments could be offered that would slow down or even stop the disease.

    A major study, called PREVENT, concentrates on people in their 40s and 50s to identify those who are at greater risk of developing Alzheimer’s . It aims to understand what is happening in their brains before symptoms appear.

    Specialised brain scans, known as PET scans, have been developed to study two proteins in the brains of those with Alzheimer’s disease. The aim is to increase the understanding of the disease process, and also to identify those people who will benefit most from new drug treatments.

    Although PET scans are sometimes used to help with a dementia diagnosis, these highly specialised scans are usually only available as part of clinical trials.

    A number of different trials are now under way in people who are currently well but are at increased risk of Alzheimer’s disease.

    What Medications Can Help

    Could a treatment for Alzheimer’s disease be in the near future?

    The FDA has approved the drug aducanumab-avwa as the first therapy that targets the fundamental pathophysiology of the disease by reducing amyloid beta plaques in the brain. It is not without controversy because of concerns it may cause swelling of bleeding in the brain.

    Some drugs curb the breakdown of a chemical in the brain, called acetylcholine, that√Ęs important for memory and learning. They may slow down how fast symptoms get worse for about half of people who take them. The effect lasts for a limited time, on average 6 to 12 months. Common side effects are usually mild for these medications and include diarrhea, vomiting, nausea, fatigue, insomnia, loss of appetite, and weight loss. There are three drugs of this type: donepezil , galantamine , and rivastigmine .

    Doctors can also prescribe medicines for other health problems that happen along with the disease, including depression, sleeplessness, and behavior problems like agitation and aggression.

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