Shaping the Future of Neurodegenerative Research at the Miller School of Medicine
Two major grants from Aligning Science Across Parkinson’s will support multisite studies examining mixed pathology and disease progression.
When Leonard Petrucelli, Ph.D., arrived at the University of Miami Miller School of Medicine in March, he brought a career shaped by decades of work across Alzheimer’s disease, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Now, two major new grants led by Dr. Petrucelli and Miller School colleagues are allowing him and his team to apply their unique insights towards large, collaborative research efforts focused on the biological complexity of Parkinson’s disease.
Dr. Petrucelli, the founding director of the Neuroscience Institute and professor in the Department of Neurology at the Miller School, is heading up a multisite team recently selected to join the Collaborative Research Network (CRN), a program of Aligning Science Across Parkinson’s (ASAP). In partnership with The Michael J. Fox Foundation for Parkinson’s Research (MJFF), ASAP has expanded the CRN to include new projects aimed at mapping the biological blueprint of Parkinson’s disease and building a standardized toolkit of global research resources needed to turn discoveries into treatments. Through a series of multi-year grants, the program aims to shorten the timeline from laboratory breakthrough to clinical application by mobilizing experts in the field to tackle high-priority research questions.
Miller School faculty are the proud recipients of two of these grants, each providing up to $9 million to support multi-site initiatives addressing the complex heterogeneity of Parkinson’s disease.
The first grant, led by Dr. Petrucelli, aims to better understand why Parkinson’s disease and Parkinson’s disease dementia often involve multiple overlapping brain pathologies and how these co-pathologies may contribute to neurodegeneration.
The second is awarded to a consortium that includes Mercedes Prudencio, Ph.D., a long-time colleague of Dr. Petrucelli who was recently appointed to the Miller School as an associate professor in the Department of Biochemistry and Molecular Biology. Dr. Prudencio and her team seek to define how multiple, interacting protein pathologies drive Parkinson’s disease progression.
“It is incredible that the Miller School is part of two distinct studies funded by ASAP,” said Dr. Petrucelli. “This extraordinary achievement reflects the strong research environment we are building here in Miami.”
A Focus on Mixed Pathology
At the center of Dr. Petrucelli’s research is the concept of mixed pathology. The term refers to the presence of multiple, disease-associated proteins in the brains of patients with Parkinson’s disease, particularly those who develop dementia.
“Although Parkinson’s disease is defined by a specific subset of pathological defects, features associated with Alzheimer’s disease are also observed in the brains of patients with Parkinson’s disease, especially Parkinson’s disease with dementia,” Dr. Petrucelli said.
This consideration reflects a broader shift in neurodegenerative research away from treating diseases as single, uniform entities. Dr. Petrucelli explained that his previous work in Alzheimer’s disease, where mixed pathology has been increasingly recognized, and ALS, which harbors some pathology similar to that seen in Parkinson’s patients, provided a natural foundation for this approach.
“I built on my work from the Alzheimer’s disease field. Our recent work was heavily invested in understanding the role of mixed pathology in this condition,” Dr. Petrucelli said. “We predicted that the methods we were applying could help expand our understanding of Parkinson’s disease. And, in fact, they do.”
Why Understanding Pathology Matters
Clinically, many neurodegenerative diseases present with overlapping symptoms, making it difficult to distinguish what is happening biologically in individual patients. Dr. Petrucelli emphasized that this limitation affects everything from diagnosis to clinical trials. Without a clear understanding of pathology or proper tools to detect the relevant pathological proteins, it is often difficult to determine which patients have mixed pathology and to what degree.
That uncertainty becomes especially problematic when patients are enrolled in drug trials.
“From a clinical trial or biomarker perspective, how do we differentiate this population?” Dr. Petrucelli said. “That’s how treatment becomes personalized. When drug therapies become available, we have to make sure they reach the right patients.”
“Personalized medicine starts by making sure patients are in the appropriate trial,” echoed Dr. Prudencio. “This feat can only be achieved when the impact of mixed pathology is recognized and addressed. Otherwise, we are leaving essential therapeutic targets on the table.”
A Collaborative, Multisite Effort
The ASAP consortium Dr. Petrucelli directs includes collaborators from The Broad Institute, the MRC Laboratory of Molecular Biology in the United Kingdom, Emory University and the University of California, Berkeley. Each member brings vital expertise to the table, along with a commitment to work together towards a common mission.
“Essentially, we’re assembling a dream team,” Dr. Petrucelli said.
The grants will be foundational for broader institutional growth and research progress that may ultimately benefit patients. Dr. Petrucelli emphasized the importance of connecting basic science with clinical expertise, particularly in movement disorders and neurology.
“The clinicians are always looking for research partners, and this is an amazing opportunity,” Dr. Petrucelli said. “The more that we uncover, the better we can develop therapies and get them to the clinicians who are treating the patients.”
The team extends to the clinical side as well. The Miller School’s Division of Movement Disorders, led by Ihtsham Haq, M.D., professor of neurology at the Miller School, follows thousands of patients with Parkinson’s disease across eight South Florida clinics and holds Center of Excellence designations from organizations including the Parkinson’s Foundation, the American Parkinson Disease Association and CurePSP.
“Mixed pathology is no abstraction for our patients. It’s only by untangling these multiple root causes that we can treat and cure these diseases,” said Dr. Haq. “We’re tremendously excited for what Dr. Petrucelli is making possible at the U.”
Looking Ahead: The Neuroscience Institute and a Future Symposium
Beyond the immediate research goals, Dr. Petrucelli sees the ASAP funding and his inclusion in the CRN as part of a larger effort to raise the national profile of neuroscience research at the Miller School. That vision also includes plans for a future symposium focused on neurodegenerative disease.
“This grant will inspire a bigger and better approach to research here at the Miller School, one that leverages this tremendous opportunity and strengthens our community. That’s what I hope to do,” he said. “Together, I believe we can make the Neuroscience Institute a leader in neurodegenerative disease research and a hub for open and productive collaboration that drives the field forward.”
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Tags: Aging Research, ALS, Alzheimer's disease, biochemistry and molecular biology, cognitive decline, Department of Biochemistry and Molecular Biology, Dr. Leonard Petrucelli, Dr. Mercedes Prudencio, Frontotemporal dementia, Neuroscience Institute, Newsroom, Parkinson's disease