The Parkinson’s Research Podcast: New Discoveries in Neuroscience

Alpha-synuclein plays a key role in the pathophysiology of Parkinson's disease, and researchers have been investigating this protein as a therapeutic target and also as a potential biomarker for the disease. The alpha-synuclein seed amplification assay, developed by Dr. Claudio Soto and colleagues, leverages the self-replicating nature of the misfolded alpha-synuclein proteins that form aggregates in Parkinson's disease. Amplifying misfolded alpha-synuclein can allow researchers and clinicians to detect the presence of the pathological form of the protein in biospecimens, even when the amount of misfolded alpha-synuclein in a sample is very low. In this episode, Claudio discusses his work in this area and how it has opened the doors for a variety of potential uses of the alpha-synuclein seed amplification assay, including applications in diagnosis, clinical trials, and drug development for Parkinson's disease.

This year, Claudio received the 2024 Robert A. Pritzker Prize for Leadership in Parkinson’s Research for his substantial contributions to research and his commitment to mentoring the next generation of scientists in the field. Claudio is the Huffington’s Distinguished University Chair, Professor of Neurology, and Director of the George and Cynthia Mitchell Center for Alzheimer’s Disease and Related Brain Disorders at The University of Texas Medical School in Houston. He is also the Founder, Vice-President, and Chief Scientific Officer at AMPRION Inc.

To help meet the growing global need for more movement disorders specialists, The Michael J. Fox Foundation created the Edmond J. Safra Fellowship in Movement Disorders in collaboration with longtime partner the Edmond J. Safra Foundation. This program supports the training of movement disorders specialists who will provide expert care and drive advances in Parkinson's research. The program is positively impacting early-career clinician-researchers, as well as the centers where they train. These impacts will continue to grow over the years as more fellows are trained. In this episode, Dr. Marcelo Merello and Dr. Sergio Castillo-Torres share their insights and perspectives as a Fellowship Director and a Fellow in the program, respectively. 

Stem cell models derived from patients with Parkinson’s disease are valuable tools that are helping researchers around the world to better understand the underlying causes of neurodegeneration and to develop biomarkers and new therapies. To maximize the potential impacts of these tools, it is critical that they are developed and shared according to the principles of open science. In her interview, Dr. Birgitt Schüle discusses her work developing alpha-synuclein cell lines, challenges and opportunities in the field, and important considerations surrounding open science. She goes in-depth on how the cell lines were developed, characterized, and deposited with the American Tissue and Cell Collection (ATCC) with funding support from The Michael J. Fox Foundation, as well as how these cells can be used to fuel future discoveries. Birgitt is an Associate Professor in the Department of Pathology at Stanford University School of Medicine and Co-Director of the Alzheimer’s Disease Research Center, Neuropathology, and Induced Pluripotent Stem Cell (iPSC) Core. 

New qualitative and quantitative tools are being developed to measure and track changes in proteins relevant for neurodegenerative disease, and these tools have the potential to accelerate drug discovery and clinical trials. In this episode, Dr. Judith Steen discusses her work creating novel qualitative and quantitative tools and workflows at the interface of proteomics and transcriptomics, including their novel FLEXI platform. This platform uses targeted, high- throughput quantitative mass spectrometry to isolate, quantify, and identify molecular changes in proteins. She describes her ongoing project, funded by The Michael J. Fox Foundation, to develop FLEXISyn, which aims to track post-translational changes in alpha-synuclein to better understand how the protein becomes dysfunctional and begins misfolding and forming toxic aggregations in Parkinson's disease. Judith is Associate Professor of Neurology at Harvard Medical School, a member of the Harvard Stem Cell Institute, and Director of the Neuroproteomics Laboratory in the F.M. Kirby Neurobiology Center at Boston Children's Hospital.

Substantial research has focused on identifying biomarkers for the diagnosis of Parkinson's disease (PD) as well as monitoring progression of the disease. In developing these biomarkers, it is critical for scientists to consider how the biomarkers will ultimately be used in the clinic and in clinical trials research. In this interview, Dr. Charles (Chuck) Adler shares his perspectives on how biomarkers are currently being used in clinical and research contexts, and what it would take for him to use them more often in clinical practice. He also discusses how groundbreaking collaborative research studies, including the Arizona Study of Aging and Neurodegenerative Disorders and the Parkinson's Progression Markers Initiative (PPMI), are having major impacts on the field. Chuck is Consultant and Professor of Neurology in the Department of Neurology and The Wayne and Kathryn Preisel Professor of Neuroscience Research at the Mayo Clinic Alix School of Medicine at the Mayo Clinic in Arizona.