Parkinson’s disease involves the degeneration of nerve cells deep in the brain, leading to slowness of movement, tremors, and impairment of cognition. The exact cause is not known, but appears to be related to the accumulation of toxic proteins called alpha-synuclein that damage dopamine pathways in the brain.
There are approximately six million people worldwide who suffer from Parkinson’s disease. Although there are therapies that can aid in walking and help reduce symptoms such as tremors, they are imperfect and do not significantly stop or delay the underlying disease processes that injure brain neurons in patients.
Experts at Brigham and Women’s Hospital (BWH) are working to understand the complex combination of effects that lead to Parkinson’s and the factors that influence the disease course once it has started. Importantly, understanding the direct molecular causes of Parkinson’s will provide a roadmap for developing novel therapeutics and lay important groundwork for future research—both here at BWH and in the broader scientific community.
The work of the Ann Romney Center for Neurologic Diseases has the potential to lead to new breakthroughs in Parkinson’s, giving hope to millions of patients and families.
“We have learned important information about Parkinson’s that should lead to new patient studies. This will bring us closer to our ultimate goal of curing the disease.” —Dennis J. Selkoe, MD, Co-director, Ann Romney Center for Neurologic Diseases
For information about Parkinson’s disease services at BWH, visit: http://www.brighamandwomens.org/Departments_and_Services/neurology/services/Parkinsons-Disease-Treatment.aspx
STEM CELL RESEARCH AND MOVEMENT DISORDERS
Stem cells can now be derived directly from a patient’s blood or skin samples to generate brain cells. Access to state-of-the-art technology allows us to edit the genomes of these cells to correct molecular defects. Such unprecedented technologies mean that precision medicine initiatives—generating treatments targeted to specific patients—are within reach for Parkinson’s Disease (PD) and related degenerative neurologic disorders. These technologies will also lead to a better understanding of the underlying mechanisms of PD and related diseases, including how toxic proteins impact brain function.
Under the direction of Vikram Khurana, MD, PhD, a team of researchers within the Ann Romney Center for Neurologic Diseases is developing stem cell-based models from patients with such disorders as PD, Multiple System Atrophy, and Spinocerebellar Ataxias. These cell models will allow researchers to investigate very early stage disease mechanisms and test potential new therapies for efficacy and safety before considering them for human trials. The overall goal of these precision medicine strategies is to provide clinician-researchers with the capability to develop and test targeted therapeutics for individual patients based on their unique stem cells and biological make-up.
THE PARKINSON’S DISCOVERY ENGINE: UNDERSTANDING DISEASE PROGRESSION
In Parkinson’s disease, as in many neurodegenerative conditions, the pace of disease progression varies considerably between patients, but the underlying mechanisms driving these differences remain poorly understood. Clemens Scherzer, MD, is working to decode the genetic architecture controlling disease progression in Parkinson’s, which will lay the groundwork for precision therapies, improving clinical trial design and heralding a new era of tailored treatment for Parkinson’s. Dr. Scherzer is working to develop genetic biomarkers that are predictive of how the disease will progress, and is partnering with pharmaceutical companies to match drugs to the specific targets identified by these markers. More aggressive inherited forms of the disease can be blocked, and mutations that slow or halt the progression of Parkinson’s—protective genes—will be targets for drugs that aim to mimic that effect. The goal is to speed potential new therapies to clinical trial and, ultimately, prevent disease progression.
A NOVEL HYPOTHESIS FOR PARKINSON’S DISEASE
For many years, researchers have been investigating the role of alpha-synuclein (α-Syn) in Parkinson’s disease and its potential as a target for therapy. Working closely with Dr. Selkoe, Tim Bartels, PhD, and his colleagues have discovered that the typical structural form of α-Syn is actually four α-Syn proteins wound together, and that this structure resists disease-associated changes. Dr. Bartels hypothesizes that, in Parkinson’s, this normal four-part structure becomes more prone to disassembling into single units, which can then regroup into toxic assemblies that spread through the nervous system and initiate brain disease. The research team is now screening for drugs that stabilize the aggregated form of α-Syn and prevent it from unfolding, as this could potentially prevent movement impairments and other symptoms experienced by those affected with Parkinson’s disease.
MOVING TOWARD A BLOOD TEST FOR PARKINSON’S DISEASE
In a paper published in the prominent journal, Brain, a multicenter study led by Clemens R. Scherzer, MD, pointed to the possibility of an effective biomarker for early Parkinson’s disease. The study, which looked at data from BWH patients as well as two large national study cohorts, found that reduced expression levels of the alpha-synuclein (SNCA) gene—related to the Î±Syn protein implicated in disease progression—are associated with Parkinson’s. This was true even for patients in the landmark Parkinson’s Progression Marker Initiative (PPMI), which enrolls patients very early on, before symptoms have met standard diagnosis criteria. SNCA levels can be obtained from a simple blood test, creating a pathway toward earlier, improved diagnosis, more effective clinical trials, and possibly one day a cure for Parkinson’s disease.
BWH Office of Strategic Communications