Advances in Parkinson’s Disease Research and Therapeutics

GTCbio | July 20th, 2017

Parkinson’s disease, the second-most common neurodegenerative disorder affecting 2–3% of the population ≥65 years of age has seen significant developments in past few years in terms of diagnosis and therapeutics. The collaboration between the European Human Brain Project and the U.S. Brain Initiative may result in a milestone for brain related diseases just as the human genome project helped in better understanding of the genome. Recent research in the field has established the use of neuro-imaging (PET, single-photon emission CT (SPECT) and novel MRI techniques) for early and differential diagnosis. A widely used therapeutic approach is deep brain stimulation to monitor the electrical activity in the basal ganglia, and respond automatically with optimum stimulation when an abnormal signal is detected. Although Levodopa is the most effective and widely used drug, many promising drugs are under clinical trials including some that modify the disease rather than relieving the associated symptoms. Some upcoming therapies may include neuro-modulation techniques, immunotherapies, stem cell therapies, and gene-modification therapies. Use of Squalamine, a natural product; anti-aggregative or compounds modulating αSyn aggregation; and ghrelin (the hunger hormone) may emerge as novel treatment options for Parkinson’s disease. NTCELL containing pathogen-free neonatal cells from the choroid plexus in pigs, which is in early trials appears to be promising. Another approach in the development phase is cell replacement therapy that is based on the differentiation of astrocytes into dopamine producing neurons. Ongoing research and emerging results have the potential to benefit millions of people worldwide.

Accumulation of α-synuclein (ASYN) plays a key role in the pathogenesis of Parkinson’s disease (PD) and other synucleinopathies. Recent findings have revealed tight reciprocal relationships between autophagy and neuroinflammation such that not only does failure in autophagy lead to protein accumulation and neuroinflammation, but also ASYN-invoked inflammation leads to failure of neuronal autophagy, resulting in a self-propagating pathological process. In addition, mutations of the glucocerebrosidase (GBA) gene represent the most important risk factor for Parkinson’s disease). These mutations lead to a decrease in GBA1 enzyme activity and have been found to be associated with increased alpha-synuclein accumulation in brains from Parkinson’s disease patients. Given the compelling genetic association and underlying pathophysiology, targeting GBA1, autophagy and neuroinflammatory mechanisms to modulate alpha-synuclein seems to be an attractive strategy for treating Parkinson’s disease.

The Stable Isotope Labeling Kinetics (SILK) platform enables the testing of Parkinson’s drugs in vivo to determine the effects of drugs on the CNS and other systems in the body. This information is beneficial as a therapeutic biomarker in early clinical development. More recently, work has begun to investigate the potential for alpha-synuclein kinetics to also serve as an early biomarker for Parkinson’s disease. Intriguingly, recent studies suggest that Parkinson’s disease may have its beginnings in the gut and spreads to the brain via the vagus nerve.

Some of the above mentioned scientific findings and technologies will be discussed at GTCbio’s CNS diseases summit to be held on September 11-12, 2017 in Boston, MA. The following speakers will discuss about “Advances in Parkinson’s disease research & therapeutics” as part of the 11th Neurodegenerative Diseases Research & Development Conference.

   •     Gayathri Ramaswamy, Lab Head, Internal Medicine Research Unit, Pfizer Inc.

Dr. Ramaswamy is the Lab Head, Senior Principal Scientist at Pfizer’s Neuroscience Research Unit. She is leading the drug discovery programs targeting apolipoprotein E (apoE) for treating Alzheimer’s disease (AD) and targeting glucocerebrosidase (GBA) for treating Parkinson’s disease (PD). Her research includes interrogating the role of lipids and lysosomes in neurodegeneration. She has more than 18 years of experience in lipid metabolism. She will talk about “Targeting Glucocerebrosidase for Parkinson’s Disease”.

   •     Malu Tansey, Associate Professor, Physiology, Emory University

Dr. Tansey has obtained her B.S/M.S in Biological Sciences from Stanford University, and her Ph.D. in Cell Regulation from UT Southwestern in Dallas, Texas. Her major area of research includes neuroinflammation, neuroimmunology and neuroscience. She investigated the cellular and molecular mechanisms underlying neuroinflammation in age-related neurodegenerative and neuropsychiatric disorders (PD, AD, and depression respectively) with the long-term goal of developing better therapeutic interventions to prevent or treat these disorders. She will talk about “Microbiome in the Gut and its role in Parkinson’s Disease”.

   •     Errol De Souza, President & Chief Executive Officer, Neuropore Therapies, Inc.

Dr. De Souza received his B.A in physiology and his Ph.D. in neuroendocrinology from the University of Toronto and postdoctoral fellowship in neuroscience from The Johns Hopkins University School of Medicine. He is an internationally recognized leader in CNS research and development. He founded Neurocrine Biosciences and has served as President and CEO for several biotech companies namely Biodel, Synaptic Pharmaceutical Corp. and Archemix. He will talk about “Targeting Autophagy and Neuroinflammatory Mechanisms to Modulate Alpha-Synuclein for the Treatment of Parkinson’s Disease”.

   •     Katrina Paumier, Assistant Professor of Neurology, Washington University School of Medicine

Dr. Paumier has completed her B.S. from University of Illinois and has received her doctorate from University of Cincinnati. She has over ten years of experience with both cellular and rodent models of Parkinson’s disease (PD). Her research has focused on understanding the role of alpha-synuclein in the pathogenesis and treatment of PD. She has begun to investigate the potential for alpha-synuclein kinetics to serve as an early biomarker for Parkinson’s disease. She will talk about “Biomarkers for PD-Stable Isotope Labeling Kinetics (SILK) Protocol to Measure the Synthesis and Clearance Rates of aSyn in CSF”.

We invite you to join us at the 11th Annual CNS Diseases Summit, to be held on September 11-12, 2017 in Boston, MA.