New Frontiers in Parkinson's Disease: From Genetics to the Clinic

• Published in: The Journal of neuroscience Vol. 38; no. 44; pp. 9375 - 9382
• Main Authors: Shihabuddin, Lamya S, Brundin, Patrik, Greenamyre, J Timothy, Stephenson, Diane, Sardi, S Pablo
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 31.10.2018
• Subjects: alpha-Synuclein - genetics; alpha-Synuclein - metabolism; Animals; Antiparkinson Agents - administration & dosage; Clinical Trials as Topic - methods; Design optimization; Drug Delivery Systems - methods; Drug Delivery Systems - trends; Drug development; Genetics; Glucosylceramidase; Humans; Kinases; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - metabolism; LRRK2 protein; Medical treatment; Movement disorders; Mutation - drug effects; Mutation - physiology; Neurodegenerative diseases; Parkinson Disease - drug therapy; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson's disease; Partnerships; Substrates; Symposium and Mini-Symposium; Synuclein; Parkinson's disease; disease-modifying therapies; alpha-synuclein; LRRK2; GBA
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.1666-18.2018

The greatest unmet therapeutic need in Parkinson's disease (PD) is a treatment that slows the relentless progression of the symptoms and the neurodegenerative process. This review highlights the utility of genetics to understand the pathogenic mechanisms and develop novel therapeutic approaches for PD. The focus is on strategies provided by genetic studies: notably via the reduction and clearance of α-synuclein, inhibition of LRRK2 kinase activity, and modulation of glucocerebrosidase-related substrates. In addition, the critical role of precompetitive public-private partnerships in supporting trial design optimization, overall drug development, and regulatory approvals is illustrated. With these great advances, the promise of developing transformative therapies that halt or slow disease progression is a tangible goal.