The Parkinson’s Research Podcast: New Discoveries in Neuroscience

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.

Sleep disturbances, such as insomnia, sleep fragmentation, excessive daytime sleepiness, and REM sleep behavior disorder are common in people with Parkinson's disease (PD). Poor sleep quality can also impact other domains of function, including motor function. Prior research has shown that a type of photoreceptor cell in the retina, called melanopsin cells, provide the main light signals to the brain to initiate sleep, and function of these cells is impaired in PD. Dr. Beatix Feigl and her colleagues developed a novel light therapy intervention that selectively activates the melanopsin photoreceptor cells, and in this episode, she discusses the results of a recent randomized controlled trial evaluating the efficacy of this melanopsin photoreceptor-directed light therapy on sleep and circadian rhythm, as well as motor behaviors. She also discusses her earlier work on melanopsin cells that led to the development of standard measures to assess their function. Beatrix is an Ophthalmologist and an Associate Professor in the School of Biomedical Sciences and Center for Vision and Eye Research, as well as the Faculty of Health, at the Queensland University of Technology.

Though existing evidence supports that dysfunction in the clearing of cellular debris plays an important role in the development of Parkinson's disease, many unanswered questions remain regarding the mechanisms of the autophagy-lysosomal pathway involved in this process. In particular, research in the field has been limited by a lack of reliable, quantitative tests for monitoring autophagy-lysosome activity. In this interview, Dr. Zhenyu Yue describes his research investigating the cellular and molecular mechanisms for Parkinson's disease and other neurodegenerative diseases, focusing on their work examining the regulation of the autophagy-lysosomal pathway, potential therapeutic targets, and MJFF-funded research that aims to develop sensitive, robust autophagy-lysosome assays to facilitate the discovery of biomarkers for PD using stem cell-derived neurons and biofluids. Zhenyu is the Aidekman Research Professor in the Department of Neurology and Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai. He is also the Director of the Center of Parkinson’s Disease Neurobiology and Director of Basic Research of Movement Disorders at Mount Sinai.

Evidence supports that dysfunction in the homeostasis of iron and other elements likely contributes to the pathophysiological mechanisms of Parkinson's disease, but we have yet to develop suitable elemental biomarkers for use in diagnosing and monitoring the progression of Parkinson's disease. Dr. Paul Lingor discusses his work in this area to identify patterns of bioelements in CSF that could serve as PD biomarkers. Beyond CSF, he is also examining tear fluid as a potential biomarker source that is easier to collect. In addition to work on biomarkers, Paul has been involved in developing and evaluating new treatments for Parkinson's disease. In this episode, he discusses an ongoing phase II clinical trial evaluating the ROCK inhibitor Fasudil, as well as research examining combinations of advanced therapies for people with later-stage Parkinson's disease. Paul is Professor of Neurology at the Technical University of Munich and head of the outpatient clinics for motor neuron disease and co-head of the outpatient clinics for Parkinson’s disease.