As research into new Alzheimer’s drugs spirals in multiple directions, patients are often left wondering what really works. Dr. Rudolph Tanzi, Professor of Neurology at Harvard University, was part of the team behind the ‘Alzheimer’s in a dish’ breakthrough in 2014, where scientists successfully grew human brain cells in a petri dish to better understand the mechanics of the disease. He tells Being Patient it’s time drug regulators lowered the bar for testing new treatments to catch Alzheimer’s in patients before they show symptoms.
- Research tackling three pillars of Alzheimer’s disease – plaques, tangles and inflammation
- Tanzi’s ‘Alzheimer’s in a dish’ allows researchers to mimic the process of plaque leading to tangles
Being Patient: Scientists are trying to tackle beta amyloid plaque, tau tangles, and even inflammation. Where should research go? Do we need to tackle it all at once? Is there one area that’s getting ahead of the others?
Dr Rudolph Tanzi: In terms of curing Alzheimer’s, we have to think about those who have the pathology of Alzheimer’s with no symptoms that are on their way to disease, just like you think about a cancer patient with no symptoms but they have a tumor beginning. In that regard, you have to hit the amyloid first and I think the amyloid hypothesis has gotten a major validation from our ‘Alzheimer’s in a dish’. If you use human neurons in the right environment and grow a mini brain like we did, then sure enough, amyloid will cause the tangles, and I think that debate has been put to rest, that amyloid does trigger the rest of the disease.
If you have someone with the disease right now and you want to help them, you need to hit mainly neuroinflammation, the brain’s immune reaction to the plaques and tangles and ensuing nerve cell death. Luckily, thanks to the Cure Alzheimer’s Fund Alzheimer’s Genome Project that I direct, several years ago, we found the first gene that controls that inflammation called CD33 and now we’re well into drug discovery around that gene as well.
Being Patient: For Cure Alzheimer’s, what is your priority today?
Dr Rudolph Tanzi: Amyloid is a high priority. We have drugs already going into trials. Second priority is to take advantage of what we discovered about the genes that control inflammation, and our drug discovery there is going way better than I thought it would. It’s so important because if you have a patient with Alzheimer’s right now, you have to stop the neuroinflammation in the brain. It’s not enough to hit the amyloid. That’s too late.
Being Patient: If the drugs do work and prevent or reduce the inflammation, then is that as good as saying we have a cure?
Dr Rudolph Tanzi: It’s tough to say what a cure is. If stopping the inflammation in a patient with the disease stops the insult that’s constantly attacking the brain, which is what I believe, then the hope is – and I believe this will be the case, but it’s debatable – is that the brain’s regenerative properties will take over. The brain has an amazing ability to regenerate. I wrote about this in the book I wrote, Super Brain, it’s all about the myths that your brain just keeps going downhill and it can’t come back. It tells stories about people with strokes who have come back miraculously because of the brain’s never-ending ability to surprise you with its regenerative properties. I believe that if we stop neuroinflammation with a cocktail that also hits the amyloid plaques, and perhaps the tangles, that you give a chance for the brain to come back. Just like those old TV commercials, as soon as you stop smoking, your lungs start to come back. The brain would be 100 times that in terms of its predictive regenerative properties. That makes me optimistic, but the proof will be in the pudding.
Being Patient: How far away do you feel like we are?
Dr Rudolph Tanzi: I think we’ll have drugs that hit the amyloid soon. Within years, like a few years, but the question will be: will the FDA allow them to be used to stop Alzheimer’s disease before symptoms? We don’t know because the FDA right now is still of the mindset that you have to hit amyloid plaques and show the patient gets better cognitively. That’s not the purpose of hitting amyloid plaques. You hit amyloid plaques before they have the disease so they don’t get to the disease. But the FDA wants you to hit plaques and say they get cognitively better. It may not be possible to do that. It’s like saying, “We’re only going to go approve your cancer drug if you give this drug to a cancer patient with a 2-inch tumor”.
Being Patient: What has the ‘Alzheimer’s in a dish’ model meant for research?
Dr Rudolph Tanzi: When you use human neurons made from stem cells in a gel-like matrix that mimics the brain where those nerve cells can create networks just like they do in the brain, you actually gets plaques first and plaques cause the tangles. Stop the plaques, you stop the tangles. Now we are testing drugs 10 times faster, 10 times cheaper to say which drugs stop the amyloid and thus stop the tangles and which ones, in some cases, stop the tangles even though there’s still amyloid. We have several dozen candidate drugs now beyond the one we have going into trials that either hit amyloid and thus tangles or hit tangles even though there’s still amyloid. That wasn’t possible before. Now, we’re bringing the inflammatory component into the 3D Alzheimer’s in a dish, as well. We already have about 12 drugs that are hitting the inflammation in the midst of amyloid plaques and tangles. It’s changed everything. It’s just made everything 10 times faster, 10 times easier, 10 times cheaper.
Watch the full interview