November 30th, 2016 – New Haven， Connecticut
I was in a doctor’s office lying on my side with my knees tucked into my chest while behind me a neurologist was inserting a catheter into my spine. For forty minutes he dug around in my back extracting cerebral spinal fluid. Almost every time he reinserted that little tube it would trip a nerve that sent a jolt of pressure and electricity into one of my ass cheeks or all the way down to my feet. The discomfort kicked my tremors up into fifth gear and caused me to break out into a sweat as a sweet southern nurse practitioner tried as best she could to distract me from what was happening behind me. As I lay there while transparent goo that my body made to protect and nourish my brain was slowly being sucked from my spine I started questioning why I had volunteered for this.
Three years ago I was diagnosed with Parkinson’s disease. I was a 29 year old kid doing quite well for myself living and working in China when suddenly I became a PWPD, a Person With Parkinson’s Disease. The first time I saw the acronym PWPD I thought it had something to do with being a POW.
There is no cure for Parkinson’s disease, there aren’t even any treatments proven to slow progression. PD results from the accumulated death of dopamine producing neurons in parts of the brain that primarily control movement and mood. When you get it you have it for life and the only thing you know is that things will get worse and worse as time goes by. Given the current state of medical science my fate looked something like this; proper medication, healthy diet and regular exercise should keep me relatively normal for the next 10 years, after which I would probably undergo DBS(deep brain stimulation), to have electrodes surgically implanted into my brain which should buy me a few more good years.
But I didn’t know any of that when I was first diagnosed so initially it didn’t bother me that much, my symptoms really weren’t that bad and I believed that I could continue living as though nothing had really happened. But they don’t call this disease degenerative for nothing, over time my symptoms progressed to the point where I felt the need to take action. I moved back to Canada, giving up a promising career in China, to not only learn how best to manage my health but also to find a way to get involved in some of the research being done.
At first I didn’t really know where to turn to, no one I knew had it nor had I even heard of anyone with it outside of Muhammed Ali and that cocky kid from Back to the Future. I remembered a video of Ali lighting the torch at the Olympic Games in Atlanta and seeing his quivering hands as he lit that giant flame. Most people probably look at that moment as a defiant act of courage from this great man who had conquered the world and not let anything stop him from getting what he wanted out of life, not Joe Frazier, not the United States government, and not Parkinson’s disease. But what I, and probably a lot of PWPDs now saw when I looked back at that was the future I was doomed to live, hands trembling, frozen expression on my face, barely able to walk properly, probably reliant on a myriad of different pills just to make an appearance.
It’s not easy figuring out how to move on with life as a young man faced with that kind of fate. The thought that one day soon I was going to need a metal rod shoved into my brain just to function, that I’ll never be able to go anywhere without a loaded case of drugs handy, that I’d be spending my time going from clinic to clinic making sure that the last specialist knew what he was talking about, that not only do I not know what’s really going on inside me but no one really does, well, suffice it to say, it was a lot to take in.
So, where to go? Who to talk to? At any other time in history the best I would have been able to do is travel to the nearest specialist (or witch doctor) and rely solely on whatever ill-informed advice he or she would have had for me.
But we live in remarkable times and I realized I had more resources at my disposal than any king or emperor had ever dreamed. To the internet I went where I soon realized there were people all over the world working diligently to fix what was ailing me; patients and physicians and researchers in seemingly every corner of the world, each with their own story to tell and advice to give, and with email addresses to boot! So I began reaching out to people, telling my story and asking them if they would tell me theirs. At no other time in human history would any of what I’ve been doing been possible. Amid all the strife and conflict we seem to be surrounded by in the world today, it is important to acknowledge that we live in remarkable times.
The information age and this disease has enabled me to get my foot in the door into places I would otherwise never have been and connect me to people whose work will change the world. It has also given me the chance to observe science in action as it pushes forward a frontier of our knowledge. I have come to believe that the treatments being developed for PD not only have a very real chance of one day making this disease a thing of the past for me and others stricken with it, but have far-reaching applications that will extend to everyone and fundamentally change the human experience.
For the past five months I have toured some of the top research labs in North America and met with some of the best physicians and scientists on the planet working on this disease, below are some of the highlights from my journey.
August 19th, 2016 – San Diego, California
Just had one of the most inspiring and hopeful weekends of my life visiting the Scripps research lab working on a ground breaking new stem cell therapy for Parkinson’s.
Know that I am a natural born skeptic and that rarely does a week go by without someone bringing to my attention an article or a new study claiming some new link between X and PD or recommending some new breakthrough therapy. Also, having lived in China for six years, any mention of stem cell research immediately signals alarm bells in my head as I’ve come across dozens of clinics promising to perform all sorts of miracles with stem cells.
In my head the problem has always seemed rather simple; neurons in my brain that produce a neurotransmitter called dopamine are dead. Unlike other cells in the body, neurons do not reproduce and our bodies do not grow new ones. If those neurons are not coming back I need to either replace them or find a way to perform whatever job they were doing. Parkinson’s research to date has mostly been the latter, through a variety of drugs and procedures doctors try to mimic the effect of those dopamine producing neurons. However, the DNA that encodes the instruction manual from which those cells derive their structure and function evolved over millions of years and survived the fiercest struggle for survival the history of life on earth has ever known. We can try and figure out everything those cells do and reproduce their effects, but we will in essence be racing to catch up with everything our DNA has learned since the beginning of life. Or we can try a different approach, rather than trying to reproduce the effect those dead neurons had, we can try to re-grow those neurons and insert them in place of the dead ones. This is exactly what researchers such as the team in San Diego are now doing, using stem cells reprogrammed from your own skin cells, scientists are trying to re-grow those dead neurons and transplant them back into patient’s brains. Recently they have seen stunning results in animal models and they are hoping to push forward with the first human trials in 2018.
The people in San Diego were remarkable and I owe them a debt of gratitude. Sherrie, the nurse practitioner, who first extended me an invitation to come visit them and who has been working tirelessly to orchestrate the whole project down there. Bob, who after no more than a phone call picked me up from the airport and put me up in his beautiful beach front home and who more importantly showed me that PD might take a lot from you but that there are parts of you that it can never get at. And Andres, the lead scientists at the lab who sat with me for hours on end and patiently answered all of my ridiculous science questions. I was blown away by not only the work they are doing but by the community they have built, by the hospitality of all those involved and by the empathy and care of the people working there.
For more information on them I encourage you to go to their website here and support the work they are doing.
I returned from San Diego invigorated and decided to delve deeper into what was happening in my own community. I had recently been enrolled as a patient at the Toronto Western Hospital movement disorder clinic, the top Parkinson’s disease clinic in Canada. After a barrage of emails and thanks to a rare genetic mutation associated with PD that I carry, I was able to jump the two year waiting list and get seen. I also need to credit my Aunt Rochelle for not only helping me get seen but also through the example that her and my Uncle Lucek set in their own struggle with disease. At Toronto Western I was put under the care of Dr. Alfonso Fasano, a vibrant young Italian neurologist who took an interest in my case and helped spur my growing curiosity in all things related to brain research.
The clinic is best known for its work on deep brain stimulation, which Dr. Fasano plays a huge role in. DBS is a relatively new technique that has sent shock waves, both literal and physical, through the PD community in the last decade. Essentially they implant a metal rod into your brain and connect it to a battery implanted into your chest cavity. An electrical current gets sent that stimulates neurons and allows the person to function once again. Who would have thought that shoving a metal spike into your brain would make it work better, science is awesome.
September 25th, 2016 – Portland, Oregon
Attended the World Parkinson’s Congress held in dreary Portland, Oregon. This is the preeminent conference of its kind, held every three years, it was a mixing of worlds as patients, physicians, clinicians, media members, scientists, researchers, and big pharma all mingled in a giant conference center for three days to learn from each other. There were 5000 people in attendance and over the three days at any given moment there were at least 8 separate seminars or discussions being run, no one could go to it all so each of us had to choose what topics were most relevant to them.
I’m thankful I came into it with a good understanding of the disease as it enabled me to make informed decisions about which kind of talks to attend. I came away with a much clearer picture of what the disease is, what I have to do to mitigate further decline, and what steps I might have to take in the future. There is still a lot I do not understand but as long as I keep pursuing this I believe I’ll be able to stay ahead of this disease and gain access to the care I need. One other benefit of all this is it has allowed me to bear witness to science as it evolves. It’s important to reflect on the fact every once in a while that everything that happens to us in the world happens because of the brains we inherited, it all starts there, every thought, every feeling, everything that you are and do starts in the brain. For so long we knew absolutely nothing about it. Nothing. In less than the time I have been alive we have learned more about the brain than we have in all of recorded history combined. And it is thanks in large part to the study of whatever the hell it is that is going on in my head. I hate to keep beating on any point but it is truly astounding what we know now compared to what we knew even 20 years ago. And this is very much a rolling frontier, it has been awe inspiring getting front row tickets to watch as our knowledge of who we are expands before my eyes.
October 27th, 2016 – San Francisco, California
Toured Dr. Steven Finkbeiner’s lab at the Gladstone Institute in San Francisco. One of the big problems the scientific community faces when trying to tackle neurological disorders is that we simply do not have adequate models to test new therapies on. To date the most widely used are either petri dishes with a few brain cells in them, or animals. Because both of these are poor substitutes for our brains, few if any treatments succeed when applied to humans. On the bright side we have become very good at curing Parkinson’s in mice, too bad mice don’t even get the disease.
Dr. Finkbeiner and his lab are trying to solve this problem through the application of machine learning to disease modeling. In partnership with Google they have developed a machine that does all the lab work autonomously and takes detailed microscopic pictures of the cells at every step as they are being reprogrammed and differentiated. Algorithms then analyze those pictures and look for patterns to identify neuronal growth and characterize them with far more accuracy than any human ever could.
They are studying a variety of mutations associated with Parkinson’s disease (and other diseases) and applying a variety of environmental factors to the cell cultures to see which factors alter phenotype expression. In addition they look for genetic modifiers of PD by family based whole genome sequencing approaches. Hoping to donate some of mine and my family’s cells to their lab soon, kinda cool knowing that in a lab somewhere cells that used to be part of my body are being handled by robots and then fed through algorithms that analyze and try to figure out a way to treat this disease.
November 14th, 2016 – New York, New York
Spent the last few days in New York where I got a chance to sit down with Dr. Lorenz Studer who pioneered the major technique being used around the world to differentiate stem cells into dopamine producing cells. Also got the opportunity to sit in on a private research meeting put on by the Michael J. Fox Foundation and meet some of the people running the organization and shake hands with that brash kid himself who used to drive around on the big screen in a Delorean, where is the hover board you promised we’d have by now Michael!?
Dr. Studer was very generous with his time and patiently answered my barrage of questions in his office at the Rockefeller labs. His approach is similar to that of Dr. Loring’s lab at Scripps. Both create dopamine producing neurons by differentiating stem cells which will then be transplanted back into the patient’s brain. Both have shown remarkable results in their trials on lab rats and both are working with the FDA. Where they differ raises a lot of interesting questions about the eventual efficacy of stem cell based therapies.
There is also skepticism in the medical community as to whether any of these approaches will ultimately prove successful. This stems from the mixed results that were had from similar(though much cruder) human trials carried out in the 90’s, as well as from the fact that the putamen, the part of the brain where the cells will be placed, does not naturally house any dopaminergic cells, just the post synaptic cells so introducing neurons into an area where they are not ‘supposed’ to be may have unforeseeable consequences.
Michael J. Fox Foundation Research Talk
First I have to thank Harry McMurtry for getting me invited to this private research talk and re-introducing me to New York. Harry also served as further proof to me that outlook and attitude in the face of these things matter more than any drug or therapy ever could.
I landed in New York the day after the election. The city was a buzz of disappointment, on seemingly every corner of New York people were gathered together trying to make sense of what just happened or finding some way to vent their frustration. I walked by Trump Tower and watched hordes of people on the verge of letting their anger boil over into violence. On more than one occasion I overheard someone say that the atmosphere of the city was akin to that following 9/11. Now that is probably a little hyperbolic, but nonetheless New York put on quite the show for me that weekend as I got to watch an entire city coming to grips with the realization that the disconnect between themselves and large swaths of the country was larger than they had believed.
The research talk put on by MJFF was a welcome retreat from what the city was going through. Not only did I get to meet some of the leaders in the PD community but I also got to hear from researchers and physicians at the forefront of new therapies. It was clear that the two hours allotted to the speakers was not nearly enough time to talk about all that is going on in Parkinson’s disease research. There are so many people studying and trying to tackle this disease from so many different angles that one can’t help but think that something is going to strike gold soon enough. And while I suspect that there may not be any one magic bullet, watching so many people dedicate their lives to tackling a disease was a testament to the best of what we are capable of.
December 2nd, 2016 – New Haven, Connecticut
Spent the last three days at the Institute for Neurodegenerative Disorders adjacent to Yale taking part in the PPMI study funded by the Michael J. Fox Foundation. The study is the largest of its kind with the goal of finding biomarkers for the disease. To date there is no definitive test for the disease. What we have, as Michael J. Fox so eloquently puts it, is essentially a drunk test. Touch your fingers here, walk up and down here, tap your toes here. For all the advancements we have made we still rely on some pretty crude techniques to determine if what a person has is even what we call Parkinson’s disease.
I’ve taken part in a few clinical trials thus far, none have been as well run as the PPMI study. At first I was wary of putting myself through trials, the idea of willingly subjecting myself to getting poked and prodded, essentially becoming a lab rat in some scientists experiments, was unappealing on a number of different levels. I’ve come to realize not only the value to be gained to society through patient involvement in such studies but also the immediate benefit I get from actively pursuing involvement in anything PD related. To date I have been examined by over 20 neurologists and have met with scores of patients and researchers and physicians. No one has a full understanding of everything involved with diseases such as these but with every person I meet I get another piece of this puzzle. So even if it means I’ll be subjected to a few more tubes being shoved into my spine, it is well worth it.
Pursuing this has also opened my eyes to some incredible things going on in medical science and what this research might one day mean for everyone else….
PD research will change the World
Recent developments have lead to novel treatments that many researchers believe will be widely available to people with Parkinson’s within the next 5 to 10 years. But this will in essence just be a version 1.0 of these therapies, as we perfect these techniques they will be applied to other diseases in version 2.0(10 to 20 years down the road) and to otherwise seemingly healthy individuals in version 3.0(20 to 30 years out).
Our brains are a tangled mess of neurons that produce neurotransmitters which trigger electrical pulses that cascade through the brain and down our central nervous system to tell the various parts of our bodies what to do. These neural pathways are held together and supported by a vast network of different cells, each with its own unique function but all directed towards keeping you alive and functioning properly. Most of what goes on in our bodies is fairly well understood today, except the brain. There are 100 billion neurons of varying types and over 100 trillion connections between those neurons. They are responsible for everything you do and are. Until recently we have had little to no understanding of how all the different pieces fit together, but thanks in large part to the detailed study of neurological disorders we are now beginning to understand how it all works. In the years to come new tools and techniques, along with the application of machine learning, will allow researchers to probe even deeper, leading many to believe that it is only a matter of time before we have a complete picture.
What we know, through the study and treatment of neurodegenerative disorders such as Parkinson’s, Alzheimer’s, ALS, etc., is that when neurons die off or chemical signals are no longer produced beyond a certain threshold, problems arise. In Parkinson’s disease for instance, symptoms do not emerge until at least 50-80% of the dopamine producing neurons in specific parts of the brain have died. Yet everyone’s brain deteriorates over time, the spread of free radicals and accumulation of misfolded proteins that occur from the simple act of eating and breathing leads to cell death. Every single one of us has different amounts of healthy neurons in different arrangements and this is the reason why there is such variety in people’s cognitive abilities. The application of treatments being developed today to fix deficiencies in people with various diseases will one day be used in people who simply have sub-optimal levels of a particular neuron in a particular part of the brain.
The neurodegeneration that leads to neurological diseases is a byproduct of the natural aging process. Increasing awareness and understanding of the factors that contribute to aging have lead to a growing number of people in the medical community believing that we can intervene in this process and halt or even reverse aging altogether. Novel therapies are being worked on to address these problems. Some of the most exciting are…
Stem Cell Transplantation
All of these techniques are in their nascent stage and will see continual improvements over the years to come. It is conceivable that once perfected seemingly healthy people will be able to walk into a clinic, get their brains scanned, get a readout of exactly what parts of their brains have sub optimal levels and opt to augment those levels through one or more of the various techniques mentioned above.
Up till now the tools available for understanding and diagnosing most diseases have been woefully inadequate and funding for ambitious research has been lacking. However there is today more money being poured into such research and more people working on tackling them than ever. In the next decade we will gain incredible new tools to help our understanding. The most promising projects come from the European human brain project and the U.S. brain initiative that are trying to do for the brain what the human genome project did for our understanding of the genome. If successful it will give researchers unprecedented insight into how our minds are pieced together. In addition there has been an immense burst in funding for projects from private institutions like the Google developed Calico labs, the Paul Allen Institute for Brain Science, the Chan Zuckerberg Initiative, the Zuckermen mind, brain and behavior institute, the Gladstone Institute, the American Federation for Aging Research, the Buck Institute, Scripps and Sens, to name a few, not to mention all the new work being done in universities and for-profit companies throughout the world.
All of these efforts together with a growing understanding that aging itself should be classified a disease leads many experts in the field to believe that we will make more progress in the next 10 years than we made in the last 100 years combined.
Then there is the application of machine learning to our understanding of disease. When it comes down to it, the reason why we have been unable to combat many of the diseases that are still with us today is that for each one of them there are simply too many factors involved for any individual or group of people to adequately grasp. However the advent of techniques such as neural networks and their application to big data will give us access to tools that are able to take in all the factors involved and output a far more accurate description of the problems we face.
While we should continue to be skeptical of the bold proclamations made by a growing number of researchers who believe that diseases and aging in general will soon be a thing of the past, there is reason to believe that it is possible. Many dismiss the idea as either an unattainable goal or just wishful thinking, but for anyone who has seen what the last years of most people’s lives looks like, this should be reason enough to believe that life does not have to be so unforgiving.
For the time being I will continue to pursue this. It has become much more to me than just an attempt to figure out what is wrong with me. Almost every day I come across something or meet someone that makes me believe we are creating a better world for ourselves. Parkinson’s has opened my eyes to some incredible things happening in the world has which inspired a curiosity in me for the future that was the impetus for starting this blog.and given me the opportunity to become in some small way a part of all of those changes. For that it has become the best thing that ever happened to me.