Two years ago I set out to try and understand the Parkinson’s disease research landscape. I wanted to know what new therapies the world was working on, who was driving research forward, and what needed to be done to speed it all up. I have since lost count of the number of labs and conferences I have been to, and have forgotten many of the faces along the way that have helped me make sense of it all.
But there had always been a gaping hole in my mental map of the world of PD research – the role of the pharmaceutical industry. Though I knew they were how therapies got from the lab to the clinic, the mechanics of how that actually happens and the process by which decisions were made was still pretty hazy.
I finally got the opportunity to lift some of that fog last week when I was given the chance to deliver a few talks and spend a couple days with people in the neuroscience division at the headquarters of the 2nd largest pharmaceutical company in the world, F. Hoffmann-La Roche Ltd, known to most simply as Roche.
A Little History
This rather stern looking gentleman is Fritz Hoffmann-La Roche. In the late 1890’s he transformed a tiny factory on the banks of the Rhine River into one of the world’s first pharmaceutical companies. He did so by bringing together the power of industrial manufacturing with newfound techniques for extracting active chemical ingredients from raw materials. He used that combination to mass-produce a cough syrup that would be the first in a series of products which would launch an empire that now employs over 94,000 people across more than 100 countries.
Roche would be at the forefront of the most underappreciated part of the industrial revolution, the birth of standardized medicine. Ubiquitous, regulated, quality-controlled medication transformed the world by removing our dependence on local chemists (or witch doctors), and in doing so has helped billions live longer, healthier lives. All of that was made possible by our ever-expanding ability to understand, manipulate and synthetically produce the biochemistry of life.
Over the last century-plus the industry has targeted one ailment after another, and achieved some pretty remarkable feats by producing effective treatments for a long list of illnesses. However, they now face the most daunting frontier in all of medical science, degenerative brain diseases. Many have chosen to shy away from this challenge due to the unique set of problems they present: we can’t access living human tissue, we can’t accurately image what is happening, we don’t have very good models to test drugs on, most drugs we do have don’t cross the blood-brain-barrier, and the sheer complexity of the system is many times greater than anything else there is. Roche, known mainly these days as the world’s leading oncology company, is one of the few in big pharma still betting on the brain.
(Unknowingly, Roche was also an early pioneer in this field. In 1912 one of their biochemists was the first to extract and isolate L-Dopa, the gold-standard for Parkinson’s therapies. However, they didn’t see any therapeutic value in the drug at the time as it seemed to cause nothing but vomiting, so the molecule was shelved. (click here for more on the history of L-Dopa))
There is an inherent distrust from many in the public towards the industry; a distrust born out of pharma’s need to maintain a certain level of secrecy and a perception that they only care about helping people when help comes with a return on investment. Frankly, Roche did not do themselves any favors on this front by building an imposing all-white interior skyscraper for their headquarters that looms over what is otherwise a quaint European city.
But peel back the facade and what these companies really are is people, women and men working long hours to deliver the one thing that both the company and patients need to survive – effective therapies. And when it comes to neurodegenerative disorders like Parkinson’s, developing those therapies requires individuals courageous enough to stick their necks out and convince higher-ups that they have some idea of how to tackle these diseases. It is a gamble few are willing to take, especially considering the history of attempts to do so is littered with almost nothing but failure.
Whatever one may think of big pharma, when it comes to treating complex diseases no amount of yoga classes or bike rides or diets or cleansing remedies can have the impact on populations of patients that the right drug can have. And only these pharmaceutical giants are capable of bringing those drugs to the people that need them.
On that front, the Parkinson’s disease research team at Roche has managed to rally enough support to move forward with a plan that they believe will allow us to make some headway in our collective fight against PD. They have chosen as their principle drug target alpha-synuclein, the protein whose aggregation is believed to be a cause of this disease, and have partnered with Prothena to bring into development a monoclonal antibody that was generated to efficiently bind these aggregates.
Though there are still many questions surrounding alpha-synuclein and this specific antibody, the people at Roche believe it should be able to slow disease progression and, in some people, potentially stop PD in its tracks. At the very least this trial, dubbed the PASADENA study, will teach us a lot about the potential therapeutic value of this approach. (Click here to learn more about the outcomes of phase 1, or here for more information regarding the PASADENA study)
One particularly innovative aspect of the trial is that they are incorporating a wide range of measuring devices to monitor disease progression, including wearable trackers and smartphones. The field has long been looking for new ways to track the disease and so far they have had pretty encouraging results. (Click here to read more)
Industry and Academia
One major obstacle that medical research has long faced is the divide between its two major branches, academia and industry. To grossly oversimplify – academia is where our basic understanding of biology grows, where new disease models are developed, and where potential druggable targets for diseases are discovered. Industry is where that knowledge then gets tested against the constraints of the real world by studying those targets to see which are most likely to make it through clinical trial.
Much has already been said about the problems that this separation causes and why the gap between these two worlds needs to be bridged. Roche it seems has been acutely aware of these problems and have set up scientist lead teams to try and drive basic research and innovation from within. As a result, many typically academic activities are done in-house or in close collaboration with academic centers and groups.
Still, it is a complaint I often hear when talking to people on either side of the divide and more needs to be done to foster closer ties between academia and industry. One group that I believe can play a crucial role in this is the most marginalized and underutilized part of this entire field, the patients.
The Role of Patients
There is a harsh truth that the PD world has to face – no one is working on a cure. Some drugs in development have the potential to halt progression and possibly restore some symptoms for a segment of people with PD, but it will take years to figure out who to give them to and how and when to get it to them. Most research goes towards detecting and halting the disease at a very early stage, which is a worthwhile goal, but does leave me scratching my head wondering what about the seven million already diagnosed and hoping for a cure?
I have long been trying to answer what the role of patients should be in medical research. While some of us are content with being mere guinea pigs, there is much more that we could do. We may not be suited to go into the lab and start mixing chemicals, but we can and should play a role in deciding what the field’s priorities should be at all levels and across all of the various entities. We are the perfect counterweight to everyone else’s vested interests as we are the only part of this equation guaranteed to have more at stake than our next publication or patent. This goes for industry, academia, NGOs, patient organizations, policy makers and regulatory bodies. Only by giving patients an equal voice and a vote will we be able to work together towards accelerating the development of better therapies in our lifetime.
My sincere gratitude to Dr. Markus Britschgi and everyone I met at Roche for showing me around, answering my many questions, and helping me put a few more pieces of this puzzle together. I hope more institutions, companies and research centers will follow in Roche’s footsteps by proactively working to bring in patients, hear their stories, learn from their expertise, but then also take the critical next step of involving them in the decision making process.
To echo a growing creed…“No decisions about us without us”.
A brilliant summation of the chasm between Big Pharma and Acedemia that maybe only the growing multitude of PwP can bridge. But how?
The trouble with neurodegenerative disease is the sheer complexity of it in the understanding of the sufferer, compared to say…most cancer. PwP simply don’t often know what to ask for or what to support or aim for in a world where their disease is hidden primarily in an impenetrable fortress behing 400 miles of BBB. Does this vast incomprehension get in our way because we simply don’t know what to fight for?
“No decisions about us without us”
Maybe we just need a Piper? Fabulous article Ben!
There’s at least one category of “research” that falls between pharma and academia — or rather let’s call it “explorations” of entire categories of interesting neurologically-active substances that have been denied official exploration by government fiat and live in a scientific demimonde. The most common currently is the ever-more-trendy world of cannabinoids, which were all placed on the forbidden-list Schedule 1 in the US nearly half a century ago (a result of Nixon-era paranoia about what was feeding an apparent youth revolt). It’s only this year that we may see the bans come down, if only for non-THC substances like cannabidiol. Meanwhile there’s a Wild West of experiential “personal trials” growing by leaps and bounds, with some organized attempts to collect “preponderance of the anecdotes” information to at least suggest more formal paths. This will no doubt get more culturally entertaining before it gets more scientifically helpful; but no doubt both academia and pharma are closely observing.
Well-written and enlightening
Harry McMurtry (646) 306-1447
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