Michael J. Fox Foundation Awards $1 Million to Drive Critical New Research Tools and Technologies in Parkinson's Drug Development
NEW YORK, NYó As part of its mission to do whatever it takes to speed development of life-transforming treatments and a cure for Parkinsonís disease, The Michael J. Fox Foundation announced $1 million in total funding for seven research projects aiming to push forward critical research tools and new technologies to accelerate PD therapeutic development.
While new genetic and cellular targets have invigorated Parkinsonís research over the past decade, converting these discoveries into practical treatments requires deliberate and strategic investment in the development of new research technologies and tools. This pursuit is critical to attaining the Foundationís ultimate goal: transformative new treatments that will make a tangible impact on patientsí lives.
Five funded teams are working to develop improved pre-clinical disease models of PD that accurately mimic the pathology and symptoms of Parkinsonís as it arises and progresses in humans. These models are critical not only for testing potential new Parkinsonís treatments, but also for opening new therapeutic avenues to address particular clinical features of the disease.
Jim Greene, MD, PhD, of Emory University has been funded by MJFF since 2006 to develop an accurate model of gastrointestinal (GI) dysfunction, such as nausea, bloating and constipation, in Parkinsonís. These symptoms of PD are poorly understood, and there is a dearth of treatment options to address them, in part because researchers lack a model that could be used to test new therapies. Dr. Greene is heading a collaboration between neurologists and GI specialists to examine the Ďenteric nervous systemí (ENS) ó a nervous system located in the stomach and intestines that contains, in both humans and pre-clinical models, nearly as many nerve cells as the brain. With follow-on funding from MJFF, the researchers are now building on Dr. Greeneís exciting earlier results and examining the ENS in parkinsonian rodents to determine which nerve cells are damaged and thus responsible for causing the GI symptoms ó information that will dramatically speed efforts to develop therapeutic targets for new GI treatments.
Chenjian Li, PhD, of Weill Cornell Medical College was previously funded by MJFF to create the first rodent models of Parkinsonís showing progressive degeneration of dopamine neurons, as is seen in the human condition. His team successfully used bacterial artificial chromosome (BAC) technology to generate rat lines with five of the most common genetic mutations associated with PD (three alpha-synuclein lines and two LRRK2 lines).† Now J. Timothy Greenamyre, MD, PhD, of the University of Pittsburgh is collaborating with Dr. Li to characterize the alpha-synuclein modelsí neurobehavioral deficits, neurochemical alterations, dopaminergic cell loss, neuropathology and molecular features. If successful, the project could lead, for the first time, to models of PD that faithfully recapitulate various components of the human disease and, optimally, help speed the development of new treatments.
The sixth funded team, led by Albert Leentjens, MD, PhD, of Maastricht University Hospital in the Netherlands, is working to validate clinical scales that would allow doctors to accurately measure anxiety disorders in PD. Dr. Leentjens will lead an international, six-center study assessing 360 Parkinsonís patients for anxiety symptoms through a structured interview and completion of the most common anxiety rating scales. Information on disease variables, motor function, mood, and cognition will be collected. This is the largest study on anxiety disorders in Parkinsonís disease to date, and will result in the first validated description of both established and atypical anxiety syndromes in PD as well as validation of the rating scales used to measure them ó a prerequisite for the design of effective clinical studies of anxiety in PD and new treatments to alleviate this troubling symptom.
The full list of funded projects, made possible through the generous support of The Brin Wojcicki Foundation, is below. As with all MJFF awards, continued funding is dependent on the achievement of specific, pre-determined milestones. Grant abstracts and researcher biosketches for all funded awards are available through the Searchable Database of Funded Grants on the Foundationís Web site, www.michaeljfox.org.
Gastrointestinal Function in Parkinsonís Rodents
James Greene, MD, PhD, Emory University
Analysis of the Role of PPN Neurons in Postural Disturbances in a Non-human Primate Model of Parkinsonís Disease
Chantal FranÁois, PhD, HŰpital de la SalpÍtriŤre†††††††††††††††††
Characterization of E46K and A53T Alpha-Synuclein BAC Transgenic Rats
J. Timothy Greenamyre, MD, PhD, University of Pittsburgh††††††††††††††††††††††††††††††††††
A Non-human Primate Alpha-Synuclein Model of Parkinsonís Disease†††
Jeffrey Kordower, PhD, Rush University Medical Center†††
The Validation of Anxiety Scales in Parkinsonís Disease
Albert† Leentjens, MD, PhD, Maastricht University Hospital
Artificial Chromosome Transgenic Mice as Model for Progressive Parkinsonís Disease
Robert Nussbaum, MD, University of California, San Francisco††††