The Aligning Science Across Parkinson’s (ASAP) initiative is building an international network of researchers to improve our understanding of the biology underlying Parkinson's disease. Developing a better understanding of how the disease originates and progresses will, we hope, lead to new therapies. The ASAP initiative will incentivize collaboration between the existing PD research community and other researchers and will be committed to open-science practices.
Introduction Parkinson’s disease is a progressive neurodegenerative disorder characterized primarily by debilitating motor symptoms, as well as gastrointestinal distress and impaired sleep and cognition. More than six million people are known to be living with the disease, and it is the fastest growing neurodegenerative disorder worldwide (GBD 2016 Parkinson's Disease Collaborators, 2018). Like Alzheimer’s disease, Parkinson's disease (PD) is usually a disease of old age; however, many patients develop symptoms of the disease in their fourth or fifth decade – the very years that should be the prime of their lives. In the 200 years since PD was described, and despite recent decades of intense clinical work, only a few therapies have been developed to mitigate some aspects of the movement disorder. Nothing has helped to arrest or slow the progression of the disease, though not for lack of searching.
One problem is that funding for PD research is modest at best: in the United States, for example, the economic burden of PD is estimated to be $52bn per year, yet the National Institutes of Health (NIH) only spent an estimated $168 m on PD research in FY 2017 (which was just 6.5% of what it spent on neurodegenerative diseases). And although two non-profit organizations – the Michael J. Fox Foundation for Parkinson’s Research and the Parkinson’s Foundation – spent a further $108 m on PD research in FY 2017, it is estimated that 1.04 million Americans have PD, so total spending on research is about $265 per patient, which is a tiny fraction of the cost borne by the families who care for their loved ones as the disease takes its course.
The PD landscape has shifted significantly since the first genetic link to the disease was discovered in 1997. Since then, the field has experienced a revolution in our understanding of genetic contributors to the disease, which has spurred industry involvement. Among the proteins implicated by genetic studies, alpha-synuclein has been linked to PD through it presence in the Lewy bodies that are found in the substantia nigra of patients who succumb to the disease (Spillantini et al., 1998). Other genetic risk factors that have emerged from sequencing efforts include the GBA gene, which encodes a lysosomal enzyme, glucocerebrosidase; LRRK2, a protein kinase; and PINK1 and PARKIN, two genes linked to the turnover of mitochondria (reviewed in Klein and Westenberger, 2012; Billingsley et al., 2018).
Yet, even with these leads, the functional connection to the more common idiopathic form of the disease is not known. More recently we have come to recognize that the disease process may begin sometimes decades before noticeable symptoms appear, raising the possibility that early treatment might eventually prevent the most devastating aspects of PD (Postuma and Berg, 2016). There is also a growing appreciation for the involvement of non-neuronal cell types, the immune system, and peripheral organ systems. If we have learned anything so far, it is that PD is a multifaceted and complex disease, more like a spectrum disorder, that involves multiple biological systems and is triggered by both genetic and environmental factors.
Because we do not fully understand the onset and progression of PD at the molecular and cellular level, our ability to develop quantitative diagnostic assays and expand therapeutic options is hampered. Treatment has not advanced substantially since the advent of levodopa more than 40 years ago, notwithstanding the more recent invention of deep brain stimulation. Moreover, we still do not know the answers to fundamental questions about initiating factors and events, genetic risk, selective neuronal death, compensatory pathways, neuro-immune mediators, and much more.
Aligning Science Across Parkinson’s (ASAP) was conceived as a vehicle to help answer these questions. Our goal is to fund a basic research program that amplifies and coordinates the efforts of researchers around the world, both inside and outside of the existing PD community. While much valuable research is underway, an additional coordinated push, specifically on basic disease mechanisms, may yield the breakthroughs needed to develop therapies that are more than palliative and go to the core of the disease. Harnessing the talents of collaborative teams employing various techniques (such as high-resolution microscopy, single cell technologies, advanced data analysis, and stem cell and human brain organoid culture) will be critical if we are to achieve this.
Launched two years ago as a joint project of the Milken Institute Center for Strategic Philanthropy and the Sergey Brin Family Foundation, ASAP will allocate financial resources that significantly enlarge the basic science effort currently supported by the government and private foundations with the goal of understanding the underlying biology of PD. An international call for pre-proposals will be announced in October of this year. Details will be available on the ASAP website
