August 14, 2019 -- More than 10 million people worldwide are currently living with Parkinson’s disease (PD), a neurodegenerative disorder that impacts the dopamine-producing neurons in the brain. Scientists do not know exactly what causes PD, but they believe it is a combination of genetic and environmental factors. Nearly 10% to 15% of all PD cases are caused by genetic mutations. A new study aims to understand how the disease develops and how it can be treated or cured. This study, PD GENEration: Mapping the Future of Parkinson’s Disease is currently being conducted by the Parkinson’s Foundation.
On August 9, 2019, The Science Advisory Board had the pleasure of discussing PD GENEration with James Beck, PhD, Chief Scientific Officer of the Parkinson’s Foundation. The study is a first-of-its-kind initiative that offers free genetic testing for clinically relevant Parkinson’s related genes and free genetic counseling for patients to help them better understand their results.
The goals of this program are threefold. First, the Parkinson’s Foundation hopes to empower those with Parkinson’s Disease (PD) to learn whether they have a genetic form of the disease. Secondly, the study will help the PD community enter an era of precision medicine, which is becoming an increasingly important tool for clinicians. And lastly, according to Dr. Beck, this program offers a pragmatic approach that not only enables clinicians to be able to provide the right type of care, but also one that will help companies identify new therapies in the pipeline and subsequently expedite clinical trials for PD patients.
The Parkinson’s Foundation will collaborate with a number of institutions to power this study, which is available to anyone with PD and will be offered through the Parkinson’s Foundation Centers of Excellence network and Parkinson Study Group sites. Parkinson’s Foundation Centers of Excellence are medical centers with specialized teams of neurologists, movement disorder specialists, physical and occupational therapists, mental health professionals and others who are up to date on the latest PD medications, therapies and research to provide the best care. Parkinson Study Group is a non-profit group of physicians and other health care providers from medical centers in the United States, Canada and Puerto Rico experienced in the care of PD patients and dedicated to clinical research of PD. The Centers of Excellence include over 48 medical centers around the world, and Parkinson Study Group consists of a network of 132 credentialed PD Centers across North America. According to Dr. Beck, the collaboration with Parkinson Study Group “doubles [the study’s] footprint in the US.”
The Parkinson’s Foundation is partnering with Fulgent Genetics to process, sequence and store DNA samples. High quality genetic testing through clinicians provide unique set of genetic test tailored to PD. PD genes are not always easy to sequence, and Fulgent has been successful where other companies have failed. Fulgent, in collaboration with the Parkinson’s Foundation, has developed a targeted list of seven genes (GBA, LRRK2, SNCA, PRKN, PARK7, VPS35, and PINK1) relevant to PD to sequence for the study.
Dr. Beck discussed how these seven genes were selected:
“LRRK2 and GBA are the two genes where clinical development is furthest along in pharmaceutical companies. More than a half dozen companies have small molecules in development that will target these genes as potential therapies for PD, that’s clear. The remaining five are interesting because we’ve had long discussions with our steering committee and a lot of input to come up with these. But they are really the ones that are relevant to PD and potential therapies coming down the pipeline. These remain interesting targets for drug companies. But they are also the ones that are distinctly relevant and easily identified when it comes to PD. These are probably the seven most common genetic forms of PD. They drop off dramatically after LRRK2 and GBA, but they’re worthwhile to identify nevertheless. There is real interest in how they may be potential targets for future clinical trials. We are not there yet, but there has been discussion, certainly in the literature, that at some point each one has a potential therapeutic target.”
Fulgent will use state-of-the-art next generation sequencing technology to analyze the DNA samples. Dr. Beck states that Fulgent is a unique partner because they have a powerful bioinformatics pipeline, with rigorous computational tools to analyze data in a meaningful way.
Advancing clinical therapies is a key aim of the PD GENEration study in addition to empowering patients to identify if they have a genetic form of PD, then enroll in clinical trial for new therapies. Previously, genetic testing allowed Parkinson’s patients to determine if they had a LRK2 or GBA mutation, but there was no direction, guidance or next step to be followed using this information. Now, “there is something to be done” says Dr. Beck. “If people know they have a genetic form of Parkinson’s Disease then they are more likely to enroll in clinical trials that they can see benefit from.”
There are several pharmaceutical companies that have PD therapeutics in their pipelines. Currently, Sanofi has a substrate inhibitor, venglustat, in phase II trials, and Denali Therapeutics has a LRRK2 inhibitor small molecule, DNL201, in phase I testing. The Parkinson’s Foundation hopes that by helping patients identify if they have a genetic form of the disease, and encouraging them to enroll in clinical trials, the development timeline for various therapies, such as venglustat and DNL201, will be greatly accelerated.
The data collected from this study will be a crucial tool for drug discovery and disease research moving forward. Banking the DNA of participants allows for the potential of whole genome sequencing in the future. This will allow researchers to identify unique factors that can play a role in PD. According to Dr. Beck, the Parkinson’s Foundation plans to make the data available to researchers and clinicians in the future so that they can learn more about how genetics impact PD.
The hope is to make the data available for qualified researchers in about six months’ time, as the genetic analysis is just starting to roll into their systems now. For scientists the data will be made available through a portal on the Parkinson’s Foundation website and will be updated regularly with the latest data. If you are interested in working with this data, the Parkinson’s Foundation provides a number of funding opportunities with a focus on early career investigators. As the CSO, Dr. Beck appreciates the processes involved in research. “I can use that to guide how we approach funding and recognize the career structure of a scientist. I can understand the pain points and identify where support from an outside entity may be really helpful.”
Dr. Beck is a passionate professional who believes that working towards understanding the science behind PD and unique populations of patients will ultimately enable researchers to develop new therapies and equip clinicians with the information they need to provide the best care possible. He also stressed the importance of supporting young scientists who are passionate and want to study PD. His background in teaching and science communication has followed him to his current role where he supports programs that provide opportunities for young scientists to hone their communication skills.
The PD GENEration study is going to provide a more comprehensive understanding of PD for the community and help PD patients globally. The Parkinson’s Foundation is actively seeking industry partners to provide feedback as this study progresses and wants to provide something to the community as a whole. As Dr. Beck suggests, the future of PD will be “precision guidance tailored to someone’s specific disease” and this study will move us one step closer to that goal.If you have any additional questions about the PD GENEration study or would like to find out more about the Parkinson’s Foundation please visit www.parkinson.org. ”