Patients Creating Meaningful Solutions for their Own Disease




Network cluster

We live in a time of transformation in the way scientific breakthroughs are created. Or more correctly, we all feel like it is time we will be living in times in which there is a transformation in the way scientific breakthroughs are created. People are more informed then ever and the free flow of information seems like the new normal way of life. Yet still, millions of people all over the world who suffer from rare, or orphan, diseases, find themselves alone in a battle- with diseases not well understood, not well addressed, under-researched and certainly under-cured. This article is about the emergence of new tools for patients to take control over their future and  accelerate the developments of treatments and cures for their own diseases.

I first learned about the possibility of patients accelerating the development of treatments for their own conditions when I met Avi Kremer. I was then a young faculty member at the University of Pennsylvania researching the brain, and within that, many topics related to ALS — a terrifying disease that destroys the motor neurons activating the muscles leading to progressive paralysis and ultimately to death typically after only 3-5 years. There is no treatment for ALS and the only approved medication, riluzole, increases a patient’s life span by approximately 2-3 months on average. I knew, of course, all those terrible facts. But I had never met an ALS patient and never prioritized my own research agenda according to the needs of ALS patients or any other patients. Avi changed that.

Avi was diagnosed with ALS at the age of 29 years old, while an MBA student at Harvard Business School. The gap from being an MBA student at Harvard, with the world as your oyster, to being told you have 3-5 years to live and the only advice is “to make a will” was incomprehensible to Avi, and it was not comprehendible to anyone who ever met Avi. It seemed the sort of situation that would have been reasonable in the middle ages, not in the 21st century.

See Avi’s own words about starting Prize4Life

Everyone that met Avi was shocked by this gap between his youth and talents, and his prospects. I am sure Avi was too. but he was able to say the next obvious conclusion – that if we all believe that in the 21st century there should be a cure for ALS, then  we simply need to make it happen. “I am certain that there will be a cure”, Avi told me. “I am certain that the idea for it is in someone’s head right now already, he just needs to connect the dots. I want to make that happen. It will happen, I will just make it happen sooner”.

With that dream, with that spirit, Avi founded Prize4Life, a non-profit organization focused exclusively on accelerating the development of treatments, and a cure, for ALS using powerful and novel incentives. Avi was joined by Shay Rishoni, an Israeli ALS patient, and also a corporate executive, pilot, military colonel (ret.) and an Iron Man. These two have created a way for patients to create a change on their own. And on the way, they also got me, and several of my colleagues. We know that what they were planning would be more impactful than what we could do ourselves, alone in the lab.

See Shay’s own word about the responsibility for accelerating a cure for ALS

So how does a small patient-based non-profit accelerate the development of treatments for a rare disease like ALS? That was Avi’s pivotal question after his diagnosis. The answer: through bringing as many new people together as possible to combat the problem together. ALS is a scientific problem. With enough brilliant minds, it would be solved.

What tools are available to bring in new minds, new insights and new solutions?

Prize models: To achieve all of that, Prize4Life adapted the prize models-identifying the greatest barriers for development and clinical testing of ALS testing, and around each such barriers creating a prize program that attracts people to solve it. Prize4Life’s prize model is inspired by similar programs such as X-prize for space travel, demonstrated to foster meaningful research. These programs raise awareness and bring new minds into a field and generate measurable results for well-defined goals. Prize4Life wants to bring all these benefits to ALS – awareness, new minds and measurable, highly needed, results – prize programs where the real prize is Life.

Prize4Life aspires to span broad fields of innovation for their importance for ALS: we gave a $1M prize for a medical device that serves as a biomarker for ALS, another prize for developing algorithms that can predict disease progression and we are running a prize for a druggable cure. We believe that biologists, chemists, engineers, clinicians, software developers and all citizen scientists can bring a meaningful change in ALS.

Open Data: Awareness is about telling researchers that ALS exists, with the hope that it would pique their curiosity. But that is not enough, as for rare disease a lot of time the problem is not the interest, but the ability to research.One of the biggest problems with rare diseases is well, the rarity. With only a few patients (one of a 1,000 individuals will die of ALS, but due to the devastatingly short life span, there are only 30,000 ALS patients in the USA right now), it is hard to gather enough information about the disease. For rare diseases, many basic questions go unaddressed due to scientists’ and clinicians’ lack of knowledge. Which patients are likely to survive more and which is less, what are the typical courses of the disease? To address these questions, data from thousands of patients is needed at any given moment. But a typical clinician, even in the largest clinics, only sees several hundred patients at most.

The solution that Prize4Life came up with is to find another source of data- data from completed ALS clinical trials. Unfortunately, all but one ALS trial have failed, with the exception being the trial to test riluzole, mentioned above. But the data collected through them still hold a great promise for better understanding ALS patients. The largest ALS clinical trials database, The PRO-ACT database, holds data from 17 clinical trials – and over 8600 patients. It is available open access and free of charge to any researcher interested. In the 2 years of its existence, more than 400 researchers have accessed it. Many of these researchers are new to ALS because until now, there was not data available for them to work on. Among the individual researchers making use of the PRO-ACT database, there are also researchers from more than 40 pharmaceutical companies, using it to drive their clinical ALS research.

Open Science: Broadly, open science is about accessing ideas from a broad array of scientists and interested but non-scientifically trained individuals – and using the collective wisdom of the crowd to solve challenging scientific problems. More specifically for us, it is the bringing together of open data and the prize models.

One of the most important things about the prize model is that it allows opening the door to news researchers – not only newindividual scientists but in some cases, a completely new type of research. For example, because of the limited availability of ALS data, it never drew much attention from the quantitative sciences. Techniques developed in machine learning, statistics, bioinformatics and medical informatics were all breaking new grounds for biomedical sciences in recent years, but not for ALS. These techniques range from requiring large samples of patients for statistical accuracy to requiring big data of millions of data points for unraveling of novel patterns of change undetected before. Amazing discoveries were made in quantitative open science through groups like Sage Bionetworks and DREAM fostering and creating world-leading standards in the creation and rigorous running of such open science initiatives. A rare disease like ALS was not part of this development, and we were determined to change that.

Therefore, before the official launch of the PRO-ACT database – before that, there was ever any large scale ALS patient data available open access for research – we teamed up with DREAM to test the power of open challenges to advance ALS research. The first ALS Challenge ran in the summer 2012. The Challenge asked solvers to use three months of patient information (from the PRO-ACT database) to predict the patient’s state 9 months later, at the end of the year.

Predictability is crucial for understanding ALS. Although the average life expectancy of an ALS patient is about three years, some people live for decades, while others succumb within months. This lack of predictability makes the design of clinical trials to discover new treatments a long, costly and complex process. An algorithm that can reduce this uncertainty would reduce the costs of ALS clinical trials by millions of dollars. We offered $50,000 as prize foran algorithm that would meet the Challenge.

The Challenge was able to attract no less than 1,000 solvers from 63 countries, working on novel methods that have the potential to reduce the costs ALS drug development by millions of dollars. In a post-Challenge survey, 80% of the solvers that answered indicated they had minimal knowledge regarding ALS before participation in the Challenge. This already demonstrates the virtue of Open Science- bringing new minds in to the field of ALS research, that can potentially create valuable solutions ( the winning solutions can reduce the costs of large scale ALS clinical trials by at least $6 million) over three months of work and in exchange for a $50,000 prize. The winning approaches are now being used in the development of several ALS treatments, and are described (and available as supplementary information) in a recent article in Nature Biotechnology, and were also covered by Science News and Science Translational Medicine.

Given this success, Prize4Life, DREAM and Sage Bionetworks are already planning the next Challenge. The ALS Stratification Challenge, opening in Summer 2015, will be a worldwide cloud-based competition designed to spur the development of quantitative solutions for developing treatments for ALS. It will be based on the full PRO-ACT database, and newly donated trials in addition that were never analyzed before. It asks the question that follows after the question of predicting ALS – not only predicting ALS progression, by identifying meaningful subgroups of patients with different disease courses and different progression rates- understanding the difference between a patient like Lou Gehrig that will only live for two year after his diagnosis, and a patient like Stephen Hawking, who has been inspiring millions for 50 years of being an ALS patient.

Open Funding: The last piece of the puzzle is open funding for the open science programs. “Crowdfunding” uses the collective financial contributions of the crowd to raise capital for innovative programs and projects that are not readily funded through traditional financing mechanisms. It democratizes science in full, and gives both patients and patient-supporters the ability to be the most important part of the solution, to choose what solutions will be created – for them!

Our Fund the Prize crowdfunding campaign raises the prize money for the ALS Stratification Challenge. It is the first of its kind effort to make the path for accelerating drug development completely open access- the patient data is open data, the research is open science and the funding is Open funding. We are already happy to have close to 100 donors from all over the world, including both researchers, ALS patients and several drug companies.

See how open funding enables open science in our Fund the Prize campaign

Supported by researchers, patients, and drug companies alike, these initiatives might well demonstrate the way drug development will look like in the not so far future. Open data, open science, open funding — Each of these concepts has the potential to enable activities that would not be possible in the closed scientific and financial worlds of the past. Together, they create a wholly new path to spurring innovation in biomedical research- a path that patients can lead themselves, and everyone can join.

Image via Smart Design / Shutterstock.

Neta Zach, PhD, MPA

Neta Zach, PhD, MPA, is scientific director at Prize4Life since 2011. She is managing the PRO-ACT database, an award winning, largest of its kind database of ALS patient data from past clinical trials, and crowdsourcing initiatives around it. Before joining Prize4Life, she was a faculty member at the University of Pennsylvania in the biology of behavior program. Prior to that Neta completed a post doctoral fellowship at Rockefeller University under a Fulbright Scholarship. Her PhD is from Hebrew University in computational neuroscience and she also holds an MPA from the University of Pennsylvania. Neta has also worked as a science journalist at the Israeli newspaper Ha’Aretz.
See All Posts By The Author

Do not miss out ever again. Subscribe to get our newsletter delivered to your inbox a few times a month.