Well, i just want to welcome you. We are still so thrilled tonight to be hosting doctor John Palfreman in conversation about his new book, brain storms the race to unlock the mysteries of parkinsons disease. His books are up for sale at the register. Also, a big thank you to the Parkinsons Institute in sunnyvale for helping us arrange this. And cspan is here filming tonight. I amim going to ask you to raise your hand if you have a question command i will bring the mic over. Professor emeritus of journalism at the university of oregon, and me, dupont, and peabody awardwinning journalist, nieman fellow, and recipient of the victor khan prize for excellence in medical science reporting. John palfreman is coauthor of the case of the frozen alex along with doctor jay william langston. The science fix director of the institute in sunnyvale, california. They coauthor, received numerous awards including the distinguished Achievement Award for modern medicine. Please help me give a warm welcome to the dr. Thank you. I learned we had parkinsons disease. Turning up in psych wards in prison cells unable to move or talk. Contracted the symptoms overnight. My colleague here cracked the case and realized there was a neurotoxin that led to a big revolution in parkinsons at the time. So i will say a few things. Thirty years. Northern california. Turned out to be a huge boon in research. Also started a whole renaissance and john read that and said this would make a great notebook. Awardwinning program. You think i would behave cigna in a sophisticated manner. After about a year i went to visit with bill in los altos. We talked about the developments in the last 25 years. I thought this was my duty as a parkinsons patient. And it has been a wonderful experience because i got to meet many neuroscientists instantly in common the share a lot with these other people and pretty sure tom isaacs walked around the coastline 4500 miles which is the equivalent of the Michael J Fox foundation and he is remarkable. Basically the exploration of parkinsons the journalist has to take care of the truth. There is always something coming around the horizon. Yes, and johns book and from my own personal view, 20 come almost 30 years really. And we had a lot of false leads. We can talk more about it later. I think we are on the threshold and can talk a little bit about issues regarding that an embedded. I think we have the corners. The jet was the talent on the size. A brilliant exercise this. And theres a lot of books that have been written on parkinsons disease. Some of them are about patients to talk about what its like to have the disease. And there really good books. And i dont want to preempt what you are going to say, but as a journalist people didnt no he had parkinsons but he basically interviewed the top 30 or 40 scientists in the world. When doctors no you have parkinsons there going to softball little bit. So he got straight information and put it together in a book where he goes between what its like to have the disease, change the thinking, pathways, dealing with it, but absolutely brilliant science and alternates more or less from chapter to chapter. My rationale for doing this was that i wanted the honest truth, no one holding back vital information. But i wasnt entirely convinced of my reasoning. Maybe i did it because i could get away with it. I told them up front i had parkinsons. On the other hand they usually avoided mentioning lab research. The truth is like many diagnose people and driven by an ever less practical desire to blend. I know the disease. But for now i think thei think the desire look normal is an important part of my therapy. Many patients would go through this sort of process. Under science parkinsons has been characterized for a long time as primarily a movement disorder. O ousi[uk it is difficult to talk about from a Patient Point of you. We have an idea of the bad actor. We think it is a mis folded protein that goes rogue which the stick hesticky comps go from cell to cell destroying them as we go. We have a model of pathology a bit like the zombie movements. The person touches they had another protein and it spread throughout the brain and that way which is given a lot of hope that disease modifying treatments to a lot of excitement. It has become kind of visit a pivotal piece entitled parkinsons disease, the tip of the iceberg. I felt when i wrote that that this can affect multiple areas in the body, the spinal cord. I thought i would get a a huge amount of lender letters from the editor, but i got accepted with them new revision and i never got one negative letter. And now we know that this disease does not affect many other areas. While it is in some ways not sounding so good, let me tell you a policy side. Before this neurologist, patients would come in and we put change their set up, but they have these other complaints. Its kind of like the waitress, its not my table. Constipation, urinary, bladder , we just didnt think that was part of our bailiwick. And now we know almost all of those are parkinsons. We are trying to develop what i call a circle of care are getting urinary bladder problems, experts in g. I. Problems, sleep disorders, and the doctors who are not just in their own specialty like a regular urologist but they really know the neurological. Parkinsons is doing this. And in outreach urologist wont even think about this. And it is different. Now we are starting to grapple with them. 80 percent of my practice now im dealing with all these other issues. Sometimes more bothersome to get sleep, up all night because there having to urinate frequently, constipation, horrible. We are dealing with that which is the good news. One of my colleagues at ucla said you know, the gps. We now know we have to deal with these things. The 2nd thing on the policy side is, many of these start before parkinsons in fact we now know a huge number of them can. Ranging from the ones john mentioned, rem sleep behavior, anxiety, depression, parkinsons my five or ten years. Now, that is a clue. If we can get early for this reckless devastation, every system needs what is called secondary prevention. So we do these words gives us a handle. In 06, so i start with a little vignette. And he said he lost his sense of smell for ten years. About five years ago hes having problems with constipation. Now he comes in because having violent behavior, the acting behavior, this part of parkinsons. See people, see doctors. And parkinsons is the 1st diagnosis. We all know that is different. It gives you a chance to get in there and do something early. The other thing is dealing with the whole disease. Any drug that helps you got to deal with the whole thing. Those things you mentioned, risk factors, what you need is a biomarker. If you had a biomarker ten years before your parkinsons is a kind of Skeptical Science journalists, i dont expect them to work totally straight off the bat, but there is good grounds for hope. The other side of it, that is what we call disease modifying therapy. The other thing that is important, help us with the symptoms, some to modifying. Extremely fortunate to have this chart levodopa although i have to say that it has been known for over 50 years and in that 5050 years we have been to the moon, sequence the human genome and invented the internet. As a patient i see this and say more should have been done. Do you agree . Fifty years and what have we cured . A better way of delivering levodopa. There is good news on that front. And i want to come back to this in a minute. Number one, one of the big problems is, it is still the best drug after 50 or 60 years, when you take a pill it peaks in about an hour and a half. And so their all these problems. It wears off, its inconsistent. And now we think upanddown, it actually works, i think, almost forever. It is just doing the ups and downs. And when the side effects it you have to cut the dose when you want more. A couple of exciting developments. What is out there, and it just came out on the market about three months ago. In this drug, we help them for ten years withten years with it. It is a castle with many little castles inside and each one dissolves a different rate. So we take it and keeps releasing levodopa. Instead of bouncing all over the place you get these nice spots and there isnow evidence if you can get that some side effects go away. That is out there right now. A lot of the companies are not covering it yet. We can work on the insurance, but you can get that right now. Now. Secondly, really interesting is inhaled levodopa. To starting the trial on that. A form now, like an inhaler and within minutes he turned on. There just talk, frozen. This could. This could be a wonderful rescue therapy, even in the best circumstances. Just start rolling patients without trial about two years ago which is another one right now. The 3rd one that i think will be the big winner, the company has a form of levodopa , you have a little box in there are tons of little needles, epidermis into the dermis. And when you put it on the measure. Straight into the bloodstream. No, no down. Side effects, therapy, if you can get that kind of continuous stimulation it goes away. Already in phase i trials in israel. I said, look, we want to be the 1st place. I think thats about a year away. That is going to be huge. They already on the trail with it. Some of these other compounds. It is a big deal. One area. The 2nd is to do with deep brain stimulation. Seems to me so far it has been a bit hit and miss. Miss. Spectacular results with some patients but not very good with others. There is wonderful closed loop systems. Instead of putting in an electrode and turning on and leaving it you have a system which weights. Membranemembrane tells me know about to termer and it kicks on and interferes with the circuit that is causing the tremor. Those kind of Adaptive Systems are coming out, and i think they are pretty interesting. The 3rd area which seems to me to be an absolute nobrainer is the important of exercise. Data and exercises so compelling that if you are a parkinsons patient you really need to do as much exercises you can. There is a concept called forced exercise. I do walks every day command she is a pacemaker, important. The speed at which you walk is incredibly productive for mortality and morbidity. If you can push yourself it is an advantage. The data always. I can tell you an interesting story. I believe that for 25 years and tell my patients exercises every bit as important as the medicines. A mile a day keeps the doctor away. And a couple years ago they came in from the university of maryland which i championed. The 1st really Scientific Study on exercise in parkinsons. You know, the others did video games, etc. 3 million. Exercise, particularly walking is the only thing that has been scientifically proven to help gate and balance which is a huge issue of parkinsons. And so the person who did it, you know, been telling my patients this for 25 years. She said,said, i wish you had told me in the 1st place. It is nice to have it. So in that study normal walking, just normal walking. Go out,. Go out, leave your front door, walk for 30 minutes and come home. It also reduces the incidence of stroke in fatal Heart Disease by 20 percent. So its a good thing to do. Do you want to talk more . So many neurodegenerative diseases, one of the big problems is it doesnt make new neurons. There is some evidence it can do that, but mostly they dont regenerate will. If all your memories are stored and neurons get kicked out with new ones there goes the memory. Its a huge handicap and treating disease. All these are due to ms. Folding proteins. And if you think of it like a towel, proteins are kind of like that, except they are folded in all different ways. As they get misfoldedmis folded the body cannot get rid of them, so they pile up. Think of it like you cannot take your garbage out of the house anymore. So that is what happens with ourselves. These proteins fold and can cause cell damage and eventually maybe cell death and for the 1st time we have approaching in parkinsons. Its called huntington approaching. A betaamyloid. Discovered through a rare family that had a mutation gene. All these and other symptoms we are talking about. When you do that, if at isnt where it is, it can be huge. Not only do i think we could stop the process of parkinsons disease but it turns out there are some areas of the brain those cells actually die. In many areas they dont. The cells are just not working. You look at the processes, they are not working, but they are still alive, still death is so overrated because a lot of times is piling up, the cells are still bare so if you can find a way to get in there, not only stopped progressing, this protein reporter we might be able to stop symptoms but sold death no. These neurons can better transport. If we get rid of that a lot of the come back. It is a social problem. The body has its own means to deal with the garbage, it gets overwhelmed. There are these Little Things there are many of them in each cell. They actually look like garbage disposals. They outlived their usefulness, kicks out of me know as since the start over and make new proteins, anybody here put artichokes than a garbage disposal, it doesnt work. That is what happens in these cells, they choke on it and cant do it. And before it hits these did garbage disposals is find a way to get rid of it. Hearken back to this, these antibodies studies, it is an exciting time. Within five years would never have said that before. The first time he announced he had parkinsons disease, it was myself, and 200 advocates and the agency the head of that, i couldnt believe, with enough money you could solve this disease in five years and i was shocked. 10 or 15 years from now. I do think with what we have now we might be able to do it. When this hearing ended it was the first time, in people magazine, parkinson, there were so many cameras in the balcony and when the hearing ended i actually got to remember the beginning of this, george bush was president , it hit the scene. They said michael, what do you think of stem cells for parkinsons and i will never forget the response, this president said stem cells, you are asking me about stem cells, i didnt even graduate from high school. I wonder if we can take a few questions. We have a microphone. Can you tell the name . Just like it sounds. Rypier rypierre. It came on the market two weeks ago. Parkinsons, we have to have the laws about it and maybe start it is really doesnt work for everybody. Number one, switching is tricky. We only get it to rise half the time so then you have to adjust and there are only four doses. You dont have a lot of them there and it doesnt work all the time but if time, youll learn how to switch, in these tassels, were going to get better. But it is terrific. There are problems and we will work with those. Talking about solving rather than curing. Very careful about using the word cure. I say dont use it. Because clearly unless we get to the point we stop it before it gets into the brain, it never is going to be but actually curing, once it is not in the brain, the cells have died, truth cure is a long way away. Stem cells are not going to do it anytime soon. Feels sells under Ronald Reagan which he put a moratorium on, they didnt work. Sunday i think there will be an answer but most people early on are not really disabled. If we could stop it right there, and doing it before my idea is how they dont know what the symptoms are for that. And cell testing. And maybe this room suite, two of those when you go into age 50, snail testing, the doctor is in the waiting room, wont take any time, we can track the heart for earlier symptoms. As far as the annual physical. And imaging test now. Trying to find imaging agents it binds protein so you can actually see the pathology. We would have an absolute people are working very hard. I want to know, i dont know if this is folklore but i can tell you parkinsons was mainly genetic, and starting to wonder, so many people are getting it. Is it an environmental, they would have died of other things, why does it seem to be more maybe that is your question is from the heart it is now if you go back in history, it started in the 1800s. The pioneers, muscular dystrophy and parkinsons, both have opposing views, the great pandemic of 1918 came along, killed 20 million people. They got parkinsons after that so we thought was environmental. And we discovered this, molecule, a lot of things, oil tankers, you name it. Way back toward environmental. In 1997 the first true genetic form of parkinsons was discovered. Something we thought we found the cause. Of few families on earth, with parkinsons, it is a classic where rare genetic forms, where are we now . The biggest respect would be aged. Genetic environment, we have one example if we are exposed to a certain chemical, lets take another one. Head trauma, parkinsons, not that clear. A mutation in our genes causing morea risk, kind of soft. If you had the genetic change which increased and one episode of head trauma, loss of consciousness for head trauma, increased 11fold. We have not found something similar used by dry cleaners and play to that now. I think it is going to be both, genetic or environmental, you still have to have something kick it out. Theres no clear answer. 20 years ago. What is the purpose of properly foldouts in a clean in the body. Focus, first described it, you will love this. Is very important when bird starts to learn how to it goes back up, being discovered by environmental biologists, and in alzheimers disease, some of the facts, it wasnt until the genetic form came out, and parkinsons, parkinsons, we know when it is damaged, chemical or mutation in the genes, making what we do parkinsons early, two months of it. What its normal function is we still dont know. Still dont know. One of the worries about these drugs to knock it down is does it do much . We may find out for the first time when it is important for. We knew having too much is a bad thing but we dont know about how little so the answer to the question is after 20 years is still a mystery. This ray of evils you talk about. Is that what some people are referring to as a stomach pump . Subcutaneous. And we are not doing that as well. You have to make an incision and put a tube right into the small intestine. This is a gel and it has a little pump that pumps it in constantly. We are just starting we have wonderful g i dr. Parkinsons on the west coast, he will do surgery for us, the same concept, you pump in consistently, it slowly dissolves. Not as far as the stomach at all. Almost instantaneously. That is another way to do what we are talking about. The problem is the surgery, someone told the the first thing you have to be a little bit of a plumber. It is quite user friendly. We still take insulin pumps and use it. And the new one is narrow dome, the epidermal, really coming. More often than that one. Hi have a friend who has parkinsons, one of the questions my husband and i have as we continue our friendship and parkinsons continues to progress and things are more di