Physician-scientist Clemens Scherzer, MD, wants to change the future of the treatment of Parkinson’s disease. In the lab, his team focuses on predicting and preventing disease progression, and on developing precision drugs and biomarkers tailored to individual patients. Scherzer is center director for the American Parkinson’s Disease Association Center for Advanced Parkinson’s Disease Research at the Brigham, and director of the Brigham and Women’s Hospital Precision Neurology Program. He is a professor of Neurology and also leads the Harvard Biomarkers Study, which he co-founded in 2007, and serves as associate chief of the Movement Disorders Division.
Scherzer recently sat down with Brigham Clinical & Research News to discuss his research approach, the resources of the Harvard Biomarkers Study Biobank and his work to build an open science approach to change the future of Parkinson’s disease treatment.
How did you become interested in the field of neurology?
CS: My interest in how the human brain works started in high school. In medical school, I was drawn to neurology, neuroscience and psychiatry. During that time, I had a chance to work with Parkinson’s patients and became fascinated by circuit diagrams depicting how movement is coordinated in the human brain.
Why are biomarkers important for the study of Parkinson’s disease?
CS: Disease progression in Parkinson’s disease has been traditionally measured using imprecise, physical exams: a neurologist might ask a patient to tap their fingers, walk down a hallway and then assigns them a score. It’s hard to determine from these assessments if a drug is working or not, as scores might vary from physician to physician, patient to patient and even hour to hour.
Over the last decades, many large-scale trials of new drugs for PD have failed or were inconclusive — we don’t know if the drug simply wasn’t working, or if we couldn’t tell because of limitations in our ability to assess a drug’s effect. When it comes to large-scale, phase 3 clinical trials of new drugs, we only have a limited number of shots on goal. This means that it’s critical during smaller, phase 2 trials to have a clear idea of which drugs are hitting their target or target pathway. For this, we need good biomarkers.
What is the overarching goal of the Harvard Biomarkers Study?
CS: We want to change the way clinical trials are done. To set the system up for success, we’re focusing on two things needed for smarter trials: identifying targeted, homogenous patient populations to participate in trials, and detecting biological markers that can indicate if we are hitting the target and changing the target pathway. Instead of going blindly into phase 3 trials and spending a lot of money for inconclusive results, we want to have a biological readout in phase 2 that helps us make a data-driven “go” or “no go” decision for moving on to phase 3.
What is the Harvard Biomarkers Study Biobank? Why is this resource so valuable for the study of neurodegenerative disease?
CS: The biobank is the rocket fuel for precision neurology: for Parkinson’s and across the entire spectrum of neurodegenerative diseases. It powers the Parkinson Discovery Engine my laboratory is building to target the disease driver in each patient with the right drug and at the right time. Until the Harvard Biomarkers Study, such a resource was not available for PD. A few years ago, I was fortunate enough to begin a collaboration with Bradley Hyman, MD, PhD, the director of the Massachusetts Alzheimer Disease Research Center at Massachusetts General Hospital. With seed funding from the Harvard Neurological Discovery Center, we launched the biobank in 2007 and have been enrolling patients ever since. Dr. Hyman’s team enrolls patients with Alzheimer’s Disease and my team enrolls patients with movement disorders, including PD. The project is a grassroots collaboration of more than 40 neurologists at the Brigham and Mass General. It’s really thanks to this partnership with neurologist colleagues that this has been a success both in recruitment and in using the samples to make new discoveries.
We take blood draws over five years and, for patients who agree, lumbar punctures. We now have more than 200,000 biosample tubes from 3,000 deeply longitudinally characterized patients. Samples allow us to characterize genome, transcriptome, and metabolome, and provide an additional benefit: we cryopreserve cells for each participant that on-demand can be made into stem cell avatars for each patient. This means that the biobank is not only an engine for discovery, but for personalized disease modeling and drug screening. Our vision is to build a search engine that identifies the disease driver in each person and suggests targeted therapies and diagnostics for each patient’s molecular blueprint.
What is the relationship between the Harvard Biomarkers Study (HBS) Biobank and the Accelerating Medicines Partnership (AMP) Knowledge Platform? What will these resources allow users to do?
CS: Right from the beginning, we’ve been interested in bringing the open science and open source movement to the field. The AMP PD Knowledge Portal makes whole genomes, and, in the near future, additional molecular data, of HBS participants publicly accessible to investigators around the world to help globally accelerate the search for cures for PD. Under the guidance of the National Institutes of Health and approved by Brigham and Women’s Hospital, this is a secure platform for accessing samples that have been de-identified to protect patient privacy.
We’ve collaborated and provided samples for 117 projects at 50 universities across the Harvard system and across the nation, as well as biotech companies. For scientists, what’s beautiful about this is they can use the portal to explore the genomic and phenotypic data, find individuals with a specific gene defect, and then go to our biobank and pull out the corresponding samples to make tailored stem cells for drug screening and to search for tailored biomarkers.