The following are my reflections on the Aligning Science Across Parkinson’s (ASAP) workshop I attended last week at the invitation of the Milken Institute Center for Strategic Philanthropy, which developed and laid the groundwork for the initiative with sponsorship from the Sergey Brin Family Foundation. Below you will also find a letter from Prof. Randy Schekman, chair of the ASAP committee and Nobel Laureate, addressed to the Parkinson’s community.
Last week, just over fifty of the world’s leading neuroscientists, biologists, and Parkinson’s researchers, along with patients, patient advocates and major funders, came together in southern California to lay the foundation for an initiative tasked with catalyzing transformational change of Parkinson’s research. That initiative is Aligning Science Across Parkinson’s (ASAP), and their mandate is clear, identify and fill the gaps in our fundamental understanding of this disease. Driving it forward, and attracting many in attendance, was the prospect of a substantial amount of funding to be put forth by the Sergey Brin Family Foundation.
Sergey’s commitment to this cause is very personal. His mother has been living with the disease for nearly 20 years, and a genetic test revealed that he is a carrier of a genetic variation associated with it. He has long been a prominent supporter of Parkinson’s research and seems ready to take a bold step forward in his commitment through this initiative.
This project has been three years in the making, and this was its largest gathering yet. I, as a patient of nearly five years, and research advocate, was fortunate enough to be invited, to contribute my opinions, and to bear witness to this historic gathering. Below are my thoughts.
I tried to go in without any pre-conceived notions about what was going to happen, but I couldn’t help but think of that promise of substantial funding as a carrot dangling in front of the room which the attendees would verbally spar over to see whose research was most worthy. While that element of competition was there to some extent, I was pleasantly surprised by a palpable recognition from everyone that widespread collaboration would be essential to truly advance our understanding of this disease.
We had been divided in the months prior into four working groups separated by area of expertise: genetics and associated biology, neuroimmunology, circuitry, and early detection. Each group was tasked with identifying the three most important knowledge gaps in their field, and coming up with a plan outlining how to fill those gaps in the years to come. Over the course of the three days the teams worked towards finalizing the presentations they had been preparing in the lead up to the workshop. At times, it felt oddly like being back in school, only my classmates were all world renowned scientists, our assignment was handed down from the co-founder of one of the largest corporations in the history of the world, and our task was to devise research plans geared toward solving degeneration in the most complex system in the universe, the human brain, which just so happened to also be going on in my specific human brain.
What struck me as I watched the working groups set to the task at hand was just how much science is driven by the opinions and beliefs of groups of individuals. Everything we know about this disease, and science for that matter, came from a thought someone had about how to make sense of something they perceived and what that implied about the nature of our world. While those beliefs are often grounded in empirical study, and are subject to rigorous scrutiny and testing, leaps of faith are made and billions of dollars and countless hours of work get spent following those beliefs.
This is especially true in modern neuroscience where there is so much unknown that we would be paralyzed if we only pursued what we knew to be true. The field seems almost completely built on beliefs; beliefs about how proteins fold, how neurons communicate, how cells die, how symptoms manifest, on and on it goes. But, watching these giants of science productively consolidate what we do know, while arguing over what we don’t, all while trying to build consensus on the best path forward, was a testament to the best of what we are capable of.
The meeting culminated in presentations from each group followed by open discussions. These were often contentious as each group’s assertions were argued and defended and at times ridiculed. While it was certainly entertaining, it also made clear just how difficult a problem Parkinson’s disease is. Listening to some of the people who know it best debate our understanding of even the most basic aspects of it, like what exactly dopamine does or what the earliest signs of the disease really are, was a stark reminder of just how little we know about what is going on in my head.
While some of the discussions were at times heated, there was a prevailing spirit of cooperation on display. The open exchange of ideas, the often expressed need to integrate the various fields of knowledge into a cohesive whole, the frustrations told over the failures of the past and the desire to help so many in need, all of which was underscored by a powerful push to overcome the barriers that hold science back. Personally, the latter is where I drew the most hope from for the future of this project. Last fall I wrote about some of the problems I saw in science, and this past March, along with fellow research advocates, I published an article in the British Medical Journal outlining specific problems in Parkinson’s disease research. This is where I saw the real opportunity for transformational change that this kind of private philanthropy can bring. Everyone seemed very cognizant of these issues and they were keen to set up a structure driven first and foremost by the urgent need to improve our understanding of this devastating disease.
However, despite all the potential that this endeavor has, there was a rather bleak takeaway for those of us living with this disease. With a few possible exceptions, the majority of what was proposed will not translate to anything clinically relevant for at least a decade, giving a certain irony to the ASAP name. I say this not is not to bemoan the organization, just to point out the reality of how difficult and time consuming what they are trying to do is. There is a lot of good reason to be excited about recent advances in the biomedical sciences, and over the course of the workshop each group presented some incredible new developments transforming our understanding of the brain. But, the transition from basic exploration to discovery to clinic is a laborious process that requires patience from us all.
I should note that there are a wide range of therapies in development that may benefit people with PD in the interim as we wait for the work of ASAP to get to the clinic. Also, this is not Sergey’s first contribution to PD research, he has long given substantial resources to the Michael J. Fox Foundation’s efforts to advance translational and early clinical-focused research. ASAP represents an even broader and deeper commitment to PD research by supporting a larger swath of work across the research continuum for PD. (Click here or here to learn more about therapies in development, or here to learn more about MJFF’s impact.)
Still, it is not the first time we in the patient community have been asked to be patient as we watch resources poured into work that likely won’t help anyone any time soon. This is particularly frustrating as many more immediately relevant questions, such as how to optimize existing therapies, or what the best diet and exercise regiments are, receive comparatively little to no support or attention.
It was also a little disappointing how little talk there was of nutrition, exercise and environmental exposure. I could be betraying my ignorance here, but I wonder if we can really understand what goes wrong in our brains without a detailed study of the nutrients that feed every cell in it, or the movements and exercises responsible for a host of neuroplastic and neurotrophic effects, or the impact of accumulated environmental exposure to toxins and pollutants (to be fair, the environment was mentioned, but only briefly). While each of those factors add even more complexity to an already incredibly complex issue, it’s hard for me to see any attempt to fill in the gaps in our understanding of PD not taking them into account and leads to a question that has been lingering in the back of my mind ever since I started delving into Parkinson’s research – Can basic science solve a problem like PD in a timescale relevant to anyone living with the disease? After all, decades of work and astronomical sums have already been poured into the basic sciences and not one person has been cured, nor do we have anything that can even slow disease progression.
That said, it is important to remember how far the basic sciences have taken us. Over the last 20 years we have seen more progress made in our understanding of the brain and what ails it than in all of human history combined. What’s more, that pace of discovery is accelerating as we now have some powerful new tools at our disposal giving us unprecedented insights into how the brain works, with more women and men working on it than ever before. Unraveling the mysteries of the human brain is our greatest challenge, and I am grateful to organizations like the Sergey Brin Family Foundation for these kinds of bold endeavors. They now have an incredibly difficult job ahead of them in taking all that was presented and debated and discussed and deciding how best to allocate the considerable resources backing this venture towards a roadmap that can deliver on the promise to catalyze transformative change in Parkinson’s research. Though that road ahead may be long and winding, it may just provide the insights needed to rid humanity of this crippling disease.
Finally, though ASAP’s focus is the basic science, they have not forgotten the people affected by this disease. The following is a letter written to the Parkinson’s community by the chair of ASAP, Prof. Randy Schekman, that he has asked me to share.
Dear Friends in the PD community,
As you have heard from Ben, the Sergey Brin Family Foundation has had a significant commitment to funding PD research. Recently this effort has extended to the development of a program on the discovery of how PD begins and spreads to the brain and beyond. Sergey’s mother has a genetic form of PD which he inherited, and his former wife, Anne, started and sustains a deep involvement in the company 23 and Me, a genetic testing service that you may have used to help identify the numerous genetic forms of PD. Sergey is committed to helping to conquer this disease that we all live with.
I am a basic scientist and have devoted my career to understanding how cells manufacture and export certain protein molecules. We now know that at least one genetic form of PD, the one that afflicts the Brin family, targets an enzyme that acts on a protein my lab discovered almost 40 years ago. Basic research has the power to uncover the secrets of nature that ultimately lead to the cures we seek for the clinic.
But my connection to PD is even more personal as my wife of 44 years died having suffered with PD for the past 20+ years.
After my wife died last year, George Pavlov, CEO of Bayshore Global Management, asked me to Chair the committee looking into a funding mechanism in support of PD research and I jumped at the opportunity to turn my grief into something positive. We just concluded an important meeting of key brain and PD scientists, and patient advocates, Ben included, where we discussed and occasionally argued about the highest priorities for this important work going forward. We reviewed the many avenues of progress on early symptoms of the disease, and the role of genetics, the immune system and brain networks in the progression of PD. Over the next months we will meet with other key funding agencies to map out a blueprint for the Brin Foundation effort to define the most important research goals and how to organize a collaborative effort to make meaningful progress.
I am committed to this program and promise you that my colleagues and I will deploy the power of basic science to discover the insights needed to develop more effective treatments and ultimately cures for the scourge of PD. In the meantime, you can help by attending to the habits of body and mind that are known to delay the progression of PD. Among these habits are a nutritious diet, regular exercise, and active engagement to stretch your brain by reading and communication with others.
I wish you well and ask that you stay tuned as our efforts go forward.
Randy Schekman
University Professor
University of California, Berkeley
Chair, Aligning Science Across Parkinson’s (ASAP) Initiative (https://parkinsonsroadmap.org/)
2013 Nobel Prize in Physiology/Medicine
Thank you, it was very interesting to read your view on this initiative.
Well done, Ben! You have explained so very well the thinking and planning of ASAP’s Initiative for us wee ones; I am so very grateful! Your statement: ‘It was also a little disappointing how little talk there was of nutrition, exercise and environmental exposure’ is something we’ve touched on before. My lay-man conclusion to this point is it’s because it becomes moot. Meaning, by the time the symptoms of a newbie PwP shows, no amount of our prior good ‘health & lifestyle’ amounts to a hill of beans in the face of this devastatingly complex disease. I even wonder…if a full brain transplant were possible, would it eventually succumb to PD?
Great work, dude!
Great to see these discussions, and more coordination is sure to be beneficial. But let me expand a bit on the note about what was NOT covered: more than just exercise and diet, but the alternative to the whole idea that medical science is solely a top-down process eventually benefitting merely-passive recipients with the fruits of our labs. In the process of patients actively dealing as best we can with our condition(s), much can be and has been learned simply by patients mindfully trying things out.
This is not just the “million monkeys with a million typewriters” alternative — that with enough patient-activists spending enough time on enough ground-up speculations and trials we will find at least some helpful procedures — but a concession to humility and serendipity. Many an important hard-science advance has begun from curiosity about an unexpected occurrence outside any lab, since these can encourage the questioning of current paradigms. The difficulty, of course, is to organize an effort to harvest and cull an ever-growing collection of self-sponsored “trials,” social media posts, crackpot articles, quasi-commercial testimonials and the rest of our chaotic PD circus. But I would think that Google, for one, could also help apply here some of the AI-based techniques that in other realms are finding unexpected patterns to pursue –actively looking, metaphorically, for the dogs that aren’t barking in anyone’s laboratories. How about it, Sergei? Can we start the Bottom-Up Institute with some seed funding, please?
I don’t see where they summarized the general ideas/directions they had in mind. I would be interested to hear/read that.
Re-reading this: It’s always a great learning curve to see things through your seasoned eyes, Ben!
I got to wondering about BBB breakdown: ‘The possibility that the BBB is leaky in AD, that is, it does not prevent the uncontrolled entry into the brain of blood proteins and other molecules, has been investigated for ∼30 years.’https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790938/
If neurodegeneration is down to this even in part, nutrients – even meds must have a different uptake, no?
It certainly would seem so, hopefully somebody somewhere out there is looking into this.
Hi Ben- I just returned from a meeting about establishing safety standards for cell replacement therapies that use pluripotent stem cells to make the specific cell types that are lost in a disease. As you know, my lab is going for the most straightforward treatment, replacing the dopamine neurons that die in people with PD with their own healthy dopamine neurons made from their iPSCs. This is not a subtle approach, like those that want to stop the remaining neurons from dying, or turning other cells into DA neurons by adding genes. Did anyone at the Brin meeting talk about replacing neurons? Yesterday I did a Facebook live Q and A on the Scripps Research Institute Facebook page: https://www.facebook.com/ScrippsResearchInstitute/
I would love to have more conversation about this approach. I’m not against conventional drugs. I just think that some diseases need an unconventional approach, like the breakthrough immunotherapy (CAR-T) treatment for cancer. I see PD the same way…if nothing else has worked, let’s try this.
Hi Jeanne, unfortunately there wasn’t much talk of cell replacement therapy, it was almost all about understanding the basic underlying disease mechanisms better. But I agree, we need some radical new approaches to really bring about transformative change.
Hey Jeanne
Don’t think we know each other – I’m a layman-researcher/writer for several years. Things have become more…tied up with my hubby of 19+years in, so I don’t do much now.
That said, iPSCs I hold in a decent chance if delivery could be overcome…much less all the other steps. I did write about this but I’ve lost my plot…where, I don’t know 🙂
With every respect to your acedemia, in your view would possible BBB-integrity loss become a factor in decline or reuptake of iPSCs?
Many thanks!
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