At the Parkinson’s Disease Foundation® (PDF®), one question above all others preoccupies us: What is the impact of the contributions we have made over the years to support research on the causes, the management and — ultimately — the cure of Parkinson’s disease (PD)?
During the half-century since our creation, we have invested more than $100 million in this research. We think it is a good time to take stock of what we have achieved to date, and how far we have to go.
We confined our analysis to the $69 million in research investments that PDF has made since the year 2000 through three signature programs: Research Center Grants; International Research Grants and Fellowships; and Career Development Awards. During this period, these programs — guided thoughtfully and strategically by an independent scientific advisory board made up of scientists, clinicians and patient advocates — supported the work of 400 scientists.
Among the questions we asked were the following: What were the major outcomes of the research? How many of the projects were successful? How many of the scientists we supported went on to receive other grants to pursue the research — among those who did, how large were these grants? How effective was the support we gave to junior scientists?
Here is an overview of the answers we found to these questions — what was our impact, what we have learned, and where we go from here to solve, treat and end Parkinson’s disease. (You can also view the poster summarizing this article here).
Supporting Scientific Teams at Academic Research Centers
Since its inception, PDF has always believed that one of the most effective models for encouraging research is found in providing long-term support to teams of scientists at leading university research centers. Currently we have three of these: Columbia University Medical Center in New York Weill Cornell Medical Center, also in New York; and Rush University Medical Center in Chicago. Together, these centers receive a total of about $3.5 million from PDF each year to support basic, clinical and translational research.
Here are some of the highpoints of the work of these centers over the years.
- Developing theories that will help solve PD by increasing our understanding of its biology. These include the “triple-hit” hypothesis, which explains how several cellular malfunctions together contribute to neurons dying in PD; the finding that underlying damage to mitochondria is evident early in the course of PD and the knowledge that alpha-synuclein may build up in nerve cells in the gut in people with PD before they develop movement symptoms.
- Developing the three critically important scales that are used to assess and monitor PD severity and that form the foundation of nearly every clinical trial in PD. These are the original Hoehn and Yahr scale, and both the original UPDRS (Unified Parkinson’s Disease Rating Scale) and its recently updated version, the MDS-UPDRS.
- Leading or collaborating in clinical trials of nearly all drugs currently used to treat PD. The list starts with the first double-blind clinical trials of Sinemet® that took place in the 1960s — to this day, the “gold standard” among anti-Parkinson’s therapies — and extends to trials for treatments now on the verge of FDA approval such as pimavanserin, the first compound to treat PD hallucinations, and carbidopa/levodopa intestinal gel, for helping to manage Parkinson’s disease motor complications.
- Laying the groundwork for innovative new therapies to ease symptoms and for potential neuroregenerative treatments that may one day reverse or end PD. The first group includes various initiatives in the emerging field of gene therapy and the second, treatments to help damaged neurons grow and restore their broken connections.
The timeline summarizes some of the major findings at centers in recent years.
Supporting the Work of Individual Scientists
PDF makes investments in the human capital necessary to advance PD research. One of the ways we do this is by investing in the innovative ideas of talented individuals through two important programs we call the International Research Grants Program (IRGP) and our Postdoctoral Fellowship Program. Through these awards, we provide necessary “seed” funding that helps talented researchers establish themselves in the profession, and tests the worth of their scientific ideas.
How do we measure the productivity of the program? One way is to see how successful the investigators are in leveraging the support that is provided by PDF into the larger and longer-term grants that are available from other programs, like those of the US National Institutes of Health (NIH).
Since 2000, PDF has supported 231 scientists through the IRGP and Fellowship programs, for a total of $11.7 million. By reviewing their careers since the PDF grant, we found that the group as a whole went on to win almost $60 million in subsequent funding for their Parkinson’s studies. In other words, for every dollar that PDF awarded through IRGP in this period, recipients were successful in raising more than $5 from NIH and other funding sources over the next several years.
Preparing Young Neurologists for Leadership in Science and Clinical Care
From the time of its founding, PDF has allocated funds to provide training to young neurologists, first at Columbia University, and later at Rush University. Through these programs, we help to train neurologists to become leaders in movement disorders who can both care for people with Parkinson’s and conduct the clinical research that will help speed new treatments. We know that when people with Parkinson’s see specialists, their care and their quality of life improves.
What happens to these investments? How well do the Fellows do, and where do they go? Since 2000, PDF has provided support for over 50 Fellows. Of these:
- Every single one still practices as a movement disorder specialist.
- 96 percent remain involved in clinical research.
- 81 percent are engaged in mentoring younger neurologists who have an interest in movement disorders.
- 80 percent practice at large, established movement disorder centers.
- 20 percent practice in geographic areas that previously had few or no specialists.
In all, PDF remains the largest private funder of specialized movement disorders training in the United States. We are ensuring that experts are available to help people living with Parkinson’s manage their disease.
Overall, the results are encouraging. The funding provided by PDF over the past dozen years has had significant impact in such areas as improving our understanding of Parkinson’s disease; testing the safety and efficacy of new potential treatments; and preparing young scientists and clinicians for future leadership, in pushing forward the science of Parkinson’s and in managing the care of those who live with the disease.
Yet as long as the cure remains beyond our reach, PDF cannot rest. This is why over the years, we have taken on new areas of investments in research. Indeed, as we write this interim report, we are reviewing areas in which we invest our dollars — more than 90 percent of them donated by our supporters — to determine which new approaches should be explored.
In one example, we are working to incorporate the views of people touched by Parkinson’s in the design of our research programs, through the Community Choice Research Award. In a related initiative, we will continue to convene scientists to discuss emerging problems in research, such as the potential role of exercise in slowing the progression of Parkinson’s. Lastly, we are building additional funding partnerships (and extending existing ones) with other foundations and associations, in both basic and clinical science.
As we go forward with this planning, we will welcome comments and suggestions from our readers. Keep your letters coming!
With long-term support, PDF research centers at Columbia University Medical Center (CUMC), Rush University Medical Center (Rush) and Weill Cornell Medical Center (Weill Cornell) have the flexibility to build collaborations among top-notch researchers and pursue the most promising avenues of research at a rapid pace.
- 2013: Discovery that mutations in the LRRK2 gene clog cellular recycling (CUMC)
- 2013: First prospective study on Impulse Control Disorders (ICDS) and PD (Weill Cornell)
- 2012: First to demonstrate colonoscopy as potential pre-diagnosis PD biomarker (Rush)
- 2010: Dopamine Withdrawal Syndrome (DAWS) first identified in PD (Weill Cornell)
- 2010: Guiding field to consider hope for dopamine neuron restoration, Burke lab reviews work on neurons lost at PD diagnosis (CUMC)
- 2009: First mouse model developed that reproduces multiple, key features of PD progression (CUMC and Weill Cornell)
- 2008: First evidence that PD may spread from cell to cell (Rush)
- 2008: Revision of UPDRS to MDS-UPDRS (Rush)
- 2007: Multiple hit hypothesis for dopamine neuron loss (CUMC)
- 2004: ELLDOPA study first to show dose-response effect of levodopa, resulting in earlier use of the drug and improvement in symptoms (CUMC)
- 2004: Alpha-synuclein clogs cellular recycling (CUMC)
- 2002: Evidence of alpha-synuclein required for PD formation (CUMC)
- 2001: First prospective measurement of incidence of hallucinations in PD begins (Rush)
- 2000: Gene therapy first demonstrated as potential treatment for PD (Rush)
This article was originally printed in the Spring 2014 issue of the Parkinson's Disease Foundation's quarterly newsletter, News & Review.