New initiative to study Parkinson disease

Su-Chun Zhang, MD, PhD
Su-Chun Zhang, MD, PhD

Su-Chun Zhang, MD, PhD, the Steenbock Professor in Behavioral and Neural Sciences at the University of Wisconsin-Madison and Waisman Center investigator, is part of an interdisciplinary team of researchers selected by the Aligning Science Across Parkinson’s (ASAP) initiative to receive $9 million over three years for the “Parkinson5D: Deconstructing Proximal Disease Mechanisms Across Cells, Space and Progression” or PD5D project.

Parkinson’s disease (PD) is a chronic, progressive disorder of the central nervous system caused by a loss of dopamine producing cells in the brain. Symptoms of PD include tremors, limb and trunk rigidity, difficulty maintaining balance and gait, and general slowness of movement. Individuals with PD may experience difficulty completing even simple tasks, such as talking and walking.

The PD5D initiative will tackle a fundamental question: How do common genetic risk variants cause Parkinson’s disease? The program will examine proximal genetic disease mechanisms in brain cell types, brain space and disease progression. Researchers hope to map the cellular circuits of Parkinson’s disease and reveal how glitches in the genetic code may lead to changes in tens of thousands of physiologically specialized neurons and glia cells. The team will work to determine how, when, which and where brain cells are destined to malfunction. The PD5D project will translate the complex human genetics of Parkinson’s disease into proximal mechanisms in specific brain cells —in patients’ brains, in the model organism Drosophila (fruit flies), and in the lab using human pluripotent stem cell genetics.

As part of the collaborative effort, the Zhang group will engineer stem cells harboring the new Parkinson’s disease-causing genes, guide the human stem cells to specialized nerve cells, and tease out the molecular and cellular process leading to dopamine nerve cell degeneration, thus revealing the pathogenesis of Parkinson’s disease.

The PD5D project is led by Clemens Scherzer, MD, a professor of neurology at Harvard Medical School and director of the Center for Advanced Parkinson Research and Precision Neurology Program in the Department of Neurology at Brigham and Women’s Hospital

By receiving this grant, the research team joins the ASAP Collaborative Research Network, an effort to support international, multidisciplinary, multi-institutional research teams to address key knowledge gaps in the basic disease mechanisms that contribute to PD development and progression. The ASAP initiative aims to accelerate the pace of discovery in PD research. Its implementation partner The Michael J. Fox Foundation for Parkinson’s Research issued the grant.