A new Alzheimer’s drug: From advisory panel to FDA — what’s at stake here? – Harvard Health Blog
It was more than 17 years since the FDA last approved an Alzheimer's disease drug. Will Biogen's drug called aducanumab end this drought? The FDA will decide by March 2021, based on its own analysis of clinical trial data and review of the evidence by an advisory committee. How does the drug work? Aducanumab is […]

It was more than 17 years since the FDA last approved an Alzheimer's disease drug. Will Biogen's drug called aducanumab end this drought? The FDA will decide by March 2021, based on its own analysis of clinical trial data and review of the evidence by an advisory committee.

How does the drug work?

Aducanumab is a monoclonal antibody designed in the laboratory to stick to the amyloid molecule that forms plaques in the brains of people with Alzheimer's disease. Most researchers believe that plaques form first and damage brain cells, causing tau tangles to form inside, killing the cells. Once aducanumab sticks to the plaque, your body's immune system kicks in and removes the plaque, thinking it is a foreign invader. The hope and expectation is that once the plaques are removed, brain cells will stop dying, and thinking, memory, function, and behavior will stop deteriorating.

Will the FDA's decision matter?

If aducanumab works, it would be the first drug that actually slows the progression of Alzheimer's disease. This means that we might be able to turn Alzheimer's disease from a deadly disease into one that people could live with for many years, the same way people live with cancer, diabetes and HIV. / AIDS.

For researchers, this means that more than 20 years of scientific work, suggesting that removing amyloid from the brain may cure Alzheimer's disease, may be correct. But many of us began to doubt this theory, as trial after trial showed that amyloid could be cleared from the brain but the clinical progression of the disease was not altered.

So, does the drug work?

I attended the one-day FDA hearing on November 6, 2020 and also independently reviewed all publicly available data for aducanumab. There has been one small clinical trial (phase 2) to assess efficacy and side effects, and two large clinical trials (phase 3) to assess efficacy, side effects, safety, and how the drug is could be used in clinical practice. The small phase 2 study and one of the large phase 3 studies were positive, meaning the drug helped slow the decline in thinking, memory and function that is usually not possible to control. 'stop in Alzheimer's disease. The other big study was negative. Hmm… are two out of three positive studies enough? The Biogen science team had many plausible explanations as to why this study was negative.

The advisory committee, however, was not convinced. They pointed out that phase 2 studies are always positive because otherwise you wouldn't go to phase 3 so this study doesn't count. They also pointed out that while you can think of the positive Phase 3 study as the 'real' and try to understand why the negative failed (which Biogen did), you can also regard the negative study as the 'true'. true, and try to understand why the other has given positive results.

The advisory board was concerned about the "functional blindness" in both studies, as a large number of participants in the treatment group needed additional MRIs and physical exams to deal with side effects. that did not occur in the placebo group. Therefore, if you were asked to come in for an additional MRI, you knew you were taking the real medicine. This knowledge may have influenced the responses subjects and their family members gave about how they were doing, which were the main findings of the study.

Should the FDA approve it?

In determining whether a drug should be approved, many factors must be taken into account. The first is whether it works and, as noted above, questions arise as to its effectiveness. You also need to consider side effects and other burdens on patients, families, and society.

You first need an amyloid PET scan to make sure you have Alzheimer's amyloid plaques. Then, to take the drug, you need an intravenous infusion every four weeks - forever. Thirty percent of those who took the drug had reversible brain swelling and more than 10% had tiny bleeding from the brain. These side effects should be monitored closely by a team of neurology / radiology experts who understand how to monitor these events and know when to pause or stop the medication.

Another factor to consider is the size of the benefit. Here it was quite small. Looking at the two objective measurements, in the positive trial the high dose made a 0.6 point change on the Mini-Mental State Examination (MMSE) to 30 points. On the 85-point Alzheimer's Disease Rating Scale - Cognitive-13 subscale (ADAS-Cog-13), the high dose made a change of 1.4 points. In the negative trial, analogous results were -0.1 (worsening) for MMSE and 0.6 for ADAS-Cog-13.

The cost must also be taken into account; for aducanumab it is estimated to be $ 50,000 per year per patient. There are over two million people with Alzheimer's disease in the stages of mild cognitive impairment and mild dementia. If a quarter of those decide to take the drug, that's $ 25 billion each year - not including the cost of PET scans and neurology / radiology teams to monitor side effects. Since most people with Alzheimer's disease have Medicare, we'll all share that cost.

In addition, Dr Joel Perlmutter, a neurologist at the University of Washington in St. Louis and a member of the FDA advisory board, argued that if the FDA approves aducanumab, fewer people would want to participate in a trial of a new drug - and that would delay probably the approval of better drugs.

If not approved, what other treatments are there?

There are many other treatments for Alzheimer's disease that are also in development. Drugs that eliminate tau - the tangles of Alzheimer's disease - are tested. Treatments using flashing lights to induce specific brain rhythms can protect the brain. Other treatments alter the gut microbiome or other parts of the body. Drugs are under development that modify nitric oxide - a gas which has critical functions for the health of the brain. Finally, in my laboratory, we develop strategies to help people with mild Alzheimer's disease and mild cognitive impairment remember things better because, in the end, that is what matters most.

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If you’re having trouble beginning an exercise plan or following through, you’re not alone. Many of us struggle getting out of the sedentary rut, despite our best intentions.

You already know there are many great reasons to exercise—from improving energy, mood, sleep, and health to reducing anxiety, stress, and depression. And detailed exercise directives and workout plans are just a click away. But if knowing how and why to exercise was enough, we’d all be in shape. Making exercise a habit takes more—you need the right mindset and a smart approach.

While practical concerns like a busy schedule or poor health can make exercise more challenging, for most of us, the biggest barriers are mental. Maybe it’s a lack of self-confidence that keeps you from taking positive steps, or your détermination quickly flames out, or you get easily discouraged and give up. We’ve all been there at some point.

Whatever your age or fitness level—even if you’ve never exercised a day in your life —there are steps you can take to make exercise less intimidating and painful and more fun and instinctive.

Ditch the all-or-nothing attitude. You don’t have to spend hours in a gym or puissance yourself into monotonous or painful activities you hate to experience the physical and emotional benefits of exercise. A little exercise is better than nothing. In fact, adding just modest amounts of physical activity to your weekly routine can have a profound effect on your mental and emotional health.

Be kind to yourself. Research shows that self-compassion increases the likelihood that you’ll succeed in any given endeavor. So, don’t beat yourself up about your body, your current fitness level, or your supposed lack of willpower. All that will do is demotivate you. Instead, look at your past mistakes and unhealthy choices as opportunities to learn and grow.

Check your expectations. You didn’t get out of shape overnight, and you’re not going to instantly transform your body either. Expecting too much, too soon only leads to frustration. Try not to be discouraged by what you can’t accomplish or how far you have to go to reach your sport goals. Instead of obsessing over results, focus on consistency. While the improvements in mood and energy levels may happen quickly, the physical payoff will come in time.

Many of us feel the same. If sweating in a gym or pounding a treadmill isn’t your idea of a great time, try to find an activity that you do enjoy—such as dancing—or pair physical activity with something more enjoyable. Take a walk at lunchtime through a scenic park, for example, walk laps of an air-conditioned mall while window shopping, walk, run, or bike with a friend, or listen to your favorite music while you move.

Even the busiest of us can find free time in our day for activities that are important. It’s your decision to make exercise a priority. And don’t think you need a full hour for a good workout. Short 5-, 10-, or 15-minute bursts of activity can prove very effective—so, too, can squeezing all your exercise into a couple of sessions over the weekend. If you’re too busy during the week, get up and get moving during the weekend when you have more time.

The key thing to remember about starting an exercise program is that something is always better than nothing. Going for a quick walk is better than sitting on the couch; one minute of activity will help you lose more weight than no activity at all. That said, the current recommendations for most adults is to reach at least 150 minutes of moderate activity per week. You’ll get there by exercising for 30 minutes, 5 times a week. Can’t find 30 minutes in your busy schedule ? It’s okay to break things up. Two 15-minute workouts or three 10-minute workouts can be just as effective.

For most people, aiming for moderate intensity exercise is sufficient to improve your overall health. You should breathe a little heavier than normal, but not be out of breath. Your body should feel warmer as you move, but not overheated or sweating profusely. While everyone is different, don’t assume that training for a marathon is better than training for a 5K or 10K. There’s no need to overdo it.

Health issues ? Get medical clearance first. If you have health concerns such as limited mobility, heart disease, asthma, diabetes, or high blood pressure, talk with your doctor before you start to exercise.

Warm up. Warm up with dynamic stretches—active movements that warm and flex the muscles you’ll be using, such as leg kicks, walking lunges, or arm swings—and by doing a slower, easier version of the upcoming exercise. For example, if you’re going to run, warm up by walking. Or if you’re lifting weights, begin with a few light reps.

Drink plenty of water. Your body performs best when it’s properly hydrated. Failing to drink enough water when you are exerting yourself over a prolonged period of time, especially in hot conditions, can be dangerous.

There’s a reason so many New Year’s resolutions to get in shape crash and burn before February rolls around. And it’s not that you simply don’t have what it takes. Science shows us that there’s a right way to build habits that last. Follow these steps to make exercise one of them.

A goal of exercising for 30 minutes a day, 5 times a week may sound good. But how likely are you to follow through ? The more ambitious your goal, the more likely you are to fail, feel bad about it, and give up. It’s better to start with easy exercise goals you know you can achieve. As you meet them, you’ll build self-confidence and momentum. Then you can move on to more challenging goals.

Triggers are one of the confidentiels to success when it comes to forming an exercise habit. In fact, research shows that the most consistent exercisers rely on them. Triggers are simply reminders—a time of day, place, or cue—that kick off an automatic reaction. They put your routine on autopilot, so there’s nothing to think about or decide on. The alarm clock goes off and you’re out the door for your walk. You leave work for the day and head straight to the gym. You spot your sneakers addict right by the bed and you’re up and course. Find ways to build them into your day to make exercise a no-brainer.

People who exercise regularly tend to do so because of the rewards it brings to their lives, such as more energy, better sleep, and a greater sense of well-being. However, these tend to be long-term rewards. When you’re starting an exercise program, it’s important to give yourself immediate rewards when you successfully complete a workout or reach a new sport goal. Choose something you look forward to, but don’t allow yourself to do until after exercise. It can be something as simple as having a hot bath or a favorite cup of coffee.

If your workout is unpleasant or makes you feel clumsy or inept, you’re unlikely to stick with it. Don’t choose activities like running or lifting weights at the gym just because you think that’s what you should do. Instead, pick activities that fit your lifestyle, abilities, and taste.

Activity-based film games such as those from Wii and Kinect can be a fun way to start moving. So-called “exergames” that are played standing up and moving around—simulating dancing, skateboarding, soccer, bowling, or la petite balle jaune, for example—can burn at least as many kcal as walking on a treadmill; some substantially more. Once you build up your confidence, try getting away from the TV screen and playing the real thing outside. Or use a smartphone app to keep your workouts fun and interesting—some immerse you in interactive stories to keep you motivated, such as course from hordes of zombies !


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